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A few years back, there was a study saying that the caramel coloring used in colas and other products had been linked to cancer in lab rodents.  I knock back a couple or three diet sodas a day, but I know that I am not, in fact, a rodent.  To get the same amount of caramel color the lab rats got, I’d have to up my intake to about a thousand cans of soda, every day.  That’s a lot of fizzy pop for someone who spends as much time on-mic as I do.  (Order your corporate voiceover and phone menus from today!)  Not to mention the caffeine and water, as we already established.


When you hear the word “chemicals,” your mind probably goes to things synthetic and potentially harmful.  If my second-grade science teacher is to be believed — shout-out to Mr. Ezdebski — everything in our world is made of chemicals.  Everything from water to warfarin, benzine to breast milk is or is made of chemicals.  And most of them, we’re pretty cool with…at least, situationally.  it’s utterly impossible to avoid chemicals, but it’s critically important to understand how these chemicals affect us.  This can get tricky, because the 7.7 billion people on spaceship earth are all slightly different to one another.  We all know to stay away from “poisons,” like mercury, where ingesting 200 milligrams would kill you, or polonium, where 200 mgs would kill 10 million people!  There are some chemicals which only certain people are sensitive to, but those people are exquisitely sensitive, then there are some chemicals which are pretty much toxic to everybody.  Outside of individual physiology, there are criteria that determine if you’re walking on sunshine or if you’ll look and feel like death on two legs, perhaps the most important of which is your exposure to the chemical.  This basic concept of toxicology is summed up with the phrase “The dose makes the poison.”  Catchy, isn’t it?  This sensible sentence comes to us across four centuries from the physician Paracelsus.


The very first thing you must know about Paracelsus is his full name.  If you’re not sitting down, you may have to grab onto something sturdy. [sfx drumroll] Philippus Aureolus Theophrastus Bombastus von Hohenheimborn. [sfx tada] Isn’t that an amazing moniker?  Born to a chemist father in 1493, Paracelsus is sometimes called the “father” of toxicology, as well as a physician, botanist, alchemist, astrologer, and general occultist.  Paracelsus was an alchemist, though he eschewed the common goal of chrysopoeia, the creation of gold from lesser metals — “Many have said of Alchemy, that it is for the making of gold and silver. For me such is not the aim, but to consider only what virtue and power may lie in medicines.”  He was the main figure associated with Iatrochemistry, an early predecessor to pharmacology that combined alchemical and medical principles.  Paracelsus rejected Gnostic medicinal traditions like cauterizing wounds and amputating injured limbs.  He advocated instead for keeping wounds clear of infection and allowing them to heal on their own.  Revolutionary stuff, I know.  He felt that sickness and health in the body relied on the harmony of man, the microcosm, and Nature of the macrocosm.  He stressed that man must have a certain balance of minerals in their bodies, and that certain illnesses of the body had chemical remedies that could cure them.  This sounds so simple and obvious to us now, but imagine if somebody walked to you and told you you were sick because you don’t have the right amounts of the right kind of rocks in your body, you’ll tell them to get stuffed.  Paracelsus pioneered the use of chemicals and minerals in medicine, coining the name for zinc, though he spelled it with a k, which looks like a comic book sound effect.  


His original writing, which we’ve condensed down to the “the dose makes the poison soundbite,” went as follows: ‘Alle Ding sind Gift und nichts ohn’ Gift; allein die Dosis macht, das ein Ding kein Gift ist.’  Crap, the universal translator is on the fritz.  [sfx banging, whirring] All things are poison and nothing (is) without poison; only the dose makes that a thing is no poison.  In other words, it’s the amount of a substance a person is exposed to, even beyond the nature of the substance, that’s really key.  For example, a small dose of aspirin can be beneficial to a person at risk for a heart attack, thanks to its blood-thinning properties, which is why you never take OTC pain relievers before getting a tattoo, unless you want the artist to hate you.  A few aspirin will get rid of your headache with virtually no side effects.  But a bottle of aspirin will send you to the emergency room with hyperventilation, vomiting, dehydration, fever, and double vision, and can even be deadly.  And don’t get me started on the complexity of giving children aspirin.


So, how can we compare the toxicities of differing chemicals, when they can all produce varying effects, and these effects all require the intake of differing amounts?  Thankfully, science has worked out the LD50 for most things you’ll encounter.  LD50 stands for ‘lethal dose 50%’, or ‘median lethal dose.’  This is the amount of a chemical required to cause death in 50% of the animal test subjects.  We use animals for this because conducting tests where you keep going until one round kills 50% of human test subjects are really hard to get funding for.  The figures can be given for when the chemical is given orally, when it is applied to the skin, or when it is injected into the animal.  The results of these tests can then be converted into figures for humans, expressed in milligrams per kilogram of body weight.  The smaller the lethal dose and therefore the LD50 number, the more toxic the chemical.  So in this case, one would be a very lonely number indeed and two wouldn’t be much better.  The LD50 for our friend aspirin is 200mg/kg, btw.  Bonus fact: aspirin is one of the best examples of genericization, where a brand name comes to mean that brand and all other similar products.  The name became so liberally used that the Bayer company actually lost their trademark to it.


If you’ve listened to this podcast for a while or even this episode to this point, you’ll know that I tend to give good news with one hand and take with the other.  There are a number of caveats to the LD50 test.  Firstly, as mentioned, it is the dose required to kill 50% of the test subjects. Therefore, it could be said to be an inaccurate representation because it does not guarantee death – it’s possible to take more than the lethal dose and live, and take less of the lethal dose and die.  Other measurements help to fill in that gap — there’s the LDLo (Lethal Dose Low) is the lowest dose known to have resulted in fatality in testing, whilst the LD100 (Lethal Dose 100%) is the dose at which 100% of the test subjects are killed.


Another issue with the lethal dose tests, and with animal testing in general, is that, while humans are animals, animals are not humans, no matter what my couch-napping puppy tells you.  The sensitivity of animals to different chemicals varies from species to species, and can also vary from that of humans.  Take for instance the alkaloid theobromine, the chemical in chocolate that makes us so blissfully happy to eat it.  Humans can stomach around 1000mg/body weight kg of theobromine.  We don’t have to be mindful of theobromine toxicity, which could cause vomiting, diarrhea, cardiac arrhythmia, and epileptic seizures, because your  average 200g bar of milk chocolate contains a little under 300mg.  Remember, we need to get to 1000mg, or 1 gram of just the theobromine *per kilo of body weight.  So if you weigh 80kg/176lbs, you’d need to eat 267 chocolate bars.  In one sitting.  At my best, I could never defeat that many.  Compare this to dogs, who can only tolerate less than a third of what we can, and have lighter bodies paired with the ability to eat comparatively huge amounts of food, especially when they’re hurriedly wolfing down something they’re not supposed to, and it’s not all that hard for them to get to lethal levels.


Additionally, although lethal dose tests give us the comfort of quantification to cling to, the lethality *will vary from person to person, depending on age, gender, medical conditions, other chemicals in the system, and factors we can’t even begin to account for.  Plus, the lethal dose of a compound doesn’t tell us all that much about at what dose symptoms of toxicity would start to manifest.  Some chemicals may have a high lethal dose, but a low toxic dose, meaning it takes a lot to kill you, but only a little to make you wish it would.


If you find all this talk of toxicity without the soothing arpeggios of the SOAD song is giving you agitate, rest easy with a little specificity.  Sipping your morning cup of joe, which by the way gets its name from the US Sec of Navy Joe Daniels who forbade any alcohol or anything stronger than black coffee onboard in WWI?  A second cup for me (or a seventh for my hubs) may lead to jittery hands and super-spastic squirrel brain, but it would take .5oz/14g of pure caffeine to take a person out.  That’s over 100 mugs-worth, depending on the strength.  Your stomach simply couldn’t hold that quantity of liquid.  If anything, you’d probably die of water intoxication before you OD’ed.  Water intoxication?  Oh yes, drinking too much of the substance that makes up the majority of the earth’s surface and our own bodies can absolutely kill you, as many of us learned after a poorly-planned and stupidly-executed morning radio contest “hold your wee for a Wii” cost two DJs their jobs and a family their wife and mother.  But don’t fear your kitchen tap or filter pitcher.  As long as you’re not taking in much more than the one liter your kidneys can process each hour, you’ll be okay.  Also, water intoxication’s symptoms, like headache, muscle spasms, and vomiting will naturally keep you in check.


What about little water, or vodka in its native Russian?  For a healthy man, a deadly dose would be 1.25 liters of 40% alcohol, about 27 shots, in an hour, assuming he does not throw up.  Again, you’d feel so terrible in the doing of it that most people would stop.  Unless you’re a 21 year old man with all your dumbass friends making you take 21 shots when midnight hits on your birthday and now the bar *has to let you in.  If you were standing outside smoking, waiting for your ‘power hour,’ first off, stop it, your clothes stink, I can smell it from over here.  It would take .8mg of nicotine from 75 cigarettes for your life to go up in smoke.  A brief aside, did anyone else have the middle or high school experience of one of their friends excitedly explaining how you could use pure nicotine to commit the perfect murder, with no clue of where you’d get pure nicotine, or was that just my friend group?  HMU on the soc med. 


But let’s not kid ourselves.  These days, if you’re smoking, it’s probably the wacky tabaccy, the devil’s lettuce, cannabis, which it will be legal to grow where I live in T-minus 65 days, 18 hours, and 43 minutes….not that I care or anything.  You’ve heard it widely touted that you can’t really overdose on cannabis and that’s functionally true.  I’m not saying you can’t have a *very bad time with too strong a dose, and for the love of god, read the label on the edibles at least twice if you’re bad at math, but to actually do what Willy Nelson and Snoop Dogg have thus far failed to, you’d need to smoke 1,500lb/680kg…in 15 minutes.  Or you could eat it like a cow, but that would still require 48lb/22kg in your gullet at once and it’s just not going to fit, no matter how big of a buffet-destroying glutton you are.


Now that I’ve taken the stinger out of some things that are bad for you, how about making you look twice at things that are actually good for you?  An apple a day keeps the doctor away, especially if you feed him the seeds, which naturally contain cyanide, or rather they contain amygdalin, which converts into cyanide in the body.  Don’t let it worry you if the occasional apple seed slips down.  To get enough amygdalin to do you any harm, without eating more apples than is physically possible, you’d have to harvest 18 apples’ worth of seeds and even then the danger is not clear and barely present.  Seeds that are designed to be distributed by animals have tough outer coatings so the seed will survive the digestive process.  You’ll have to grind those 18 apples’ worth of seeds up in a blender and if you manage to do *that by accident…just….how?  Also, viewers of Dr. Oz — and welcome to the more responsible side of science reporting, we’re glad you’re here — may remember him kicking up a fuss and panicking mothers that they were feeding their children sippy cups of arsenic.  That was also not a danger, as FDA testing readily proved.  Personally, I try not to take medical advice from daytime TV hosts, especially ones who have been dragged before senate subcommittees.  Come for me, Mehmet.   


If cherries are more your thing, and they surely are in our household, same same but different.  Cherry pits also contain amygdalin, as do the stones of apricots, peaches, and the bitter almond stones.  They actually contain a lot more than apple seeds.  Only two or three pits can make for a lethal dose, but again the hard seed coat is a saving grace, so you’re safe as long as you don’t chew them up.  Keep a keen eye out if you’re shopping in a health food store and want something to snack on, you might find yourself with a bag of what looks like almonds, but are actually apricot kernels.  They’ll be labelled correctly, that’s not the problem.  The problem is that the label will also say something to the effect of ‘only eat 2-3 of these at a time because they contain cyanide’ and who reads the labels word for word?  It shouldn’t even be legal to sell them as food, in this reporter’s opinion.


Maybe a nice banana.  They don’t really have seeds, since the cavendish bananas in stores are clones.  And they’d got potassium, as anyone who’s had the eating of them cure muscle cramps can attest.  But you wouldn’t want too much potassium, that would give you hyperkalemia.  Hyper meaning high, kal from the periodic table of elements for potassium and emia meaning presence in blood, which can ruin your kidneys’ day.  You’d need to shove down 400 bananas on your lunch break to make that happen.  You know what else bananas have?  Radiation.   The potassium in bananas is potassium 40, which makes them very slightly radioactive.  Brazil nuts, too.  Their trees have an extensive underground root system, which absorbs radium in the soil like it’s nobody’s business.  In the case of radiation, you’ll have to eat 1000 of them, but cumulatively across your whole life.  Don’t worry, though, because I subtly stopped talking about sudden death and shifted over to micromorts.  A micromort is your risk for sudden death, presented numerically.  You’ve got a million micros before you get to mort.  Everything you do and are exposed to adds to your micromorts, from eating 1000 bananas, which increases your micromort count by one, to things like summiting Everest, which is worth 40k micromorts.  

You can hear more about micromorts in the latest bonus episode over at patreon, where I hope our newest supporters, Rick S, Jessica R, Barry S, Michael W, Alex P, Paul W, and Jellybean will enjoy that and nearly 50 others, as well as early access, ad-free episodes, and the odd surprise perk in the mail.  There’s a great clip from QI of the otherwise-brilliant Sandi Toksvig struggling to understand the danger of bananas and it never fails to delight.  I’ll put it in our groups…


If your mother told you to eat your carrots because they’re good for your eyes, A) that’s an exaggeration leftover from British war propaganda, we’ll talk about that some day, and B) we’re talking about vitamin A.  Vitamin A or retinol commonly occurs in vegetables, in the form of beta carotene, which gives things like squash and carrots their color.  It’s also found in some fish and animal flesh.  Vitamin A is a fat-soluble vitamin, meaning any surplus you take in is stored in your body fat.  If you take in too much on a regular basis, it can actually cause your skin to appear yellow or even orangish.  Your skin will also be dry and cracked, your hair thinning, your head will hurt and if you keep it up, you guessed it, you’ll die.  If you wanted to die of hypervitaminosis A more quickly, get you a dripping chunk of liver from an arctic animal, be it polar bear, moose or several kinds of seals.  That’ll kill you straight away.  Okay, then let’s grab from citrus fruit to get our vitamin C.  Vitamin C is water-soluble.  Your body takes in what it needs and you pee out the rest.  Right?  Right?!  Sorry, Charlie.  If you *really apply yourself, you *can overdose on vitamin C, but, in keeping with the theme today, you’ll have to eat 1600 oranges and I suspect the enamel on your teeth would be as soft as boiled peas before you finish.


Be mindful how you season your food, too.  The Dietary Guidelines for Americans recommends limiting sodium intake to less than 2,300 mg per day, equal to about 1 teaspoon of salt.  While we are eating substantially more than we should, at about 3400 mg per day, we’re still well under the sudden-death of a 240g/9oz/48 teaspoons.   We, modern people in general and American more specifically, also take in too much sugar.  The fatal dose of sucrose is 5 oz per pound of body weight or 64g/kg.  This means that a person weighing 160lbs would need to eat 10 5lb bags of sugar.  Though has anyone else noticed that sugar now comes in 4lb bags or smaller?  Some like it hot, but there’s a limit to everything.  129 teaspoons of pepper all at once could kill you, as would 130 teaspoons of red chili pepper flakes.  Your body would probably stop you well before you got that far, but that may not be the case with nutmeg.  As little as a few teaspoons of nutmeg can induce convulsions, palpitations, nausea and possibly death, as people seeking a cheap high find out the hard way.  I’d like to drop in a clip from Archer were Ray references nutmeg as “Malcom X tea” for a withdrawing Woodhouse, but I didn’t know how many people would recognize it.


My head is swimming, you say.  Maybe I’ll just brush my teeth and go to bed.  Okay, but whatever you do, don’t eat 24 tubes of toothpaste, or you’ll be a lethal dose of fluoride.  In case, you know, that’s a thing you were planning to do.


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Sometimes, though,the poison is the poison and the question is, how much can we feed to an unknowing public to maximize profits before people start dying en masse and someone cottons on?  As the industrial revolution gained steam, npi, and people moved off family farms and into cities and factory jobs, fewer people grew their own food, knew where their food came from, or even knew what they were truly eating.  There were no rules about listing ingredients, and anything short of cyanide was fair game.  Remember, this was the era of heroine cough syrup for children, just for context.  Common preservatives included sulfuric acid, copper sulfate, borax, which we use in the laundry, boric acid, which you may have in the form of ant-killer, and formaldehyde, most famous for preserving dead bodies.  It wasn’t uncommon for hardy candy to contain white lead.  Milk would have water added to stretch it out, formaldehyde to preserve it, chalk to make it look white again, and sometimes even pureed cow brain to simulate a head of risen cream.  Flour would be adulterated with clay and sawdust.  Your morning coffee may actually be charcoal and ground up charred animal bones.  Nothing could be trusted!  9 out of the 10 “pure maple syrup” products sold in the state of Indiana did not actually include any maple syrup.  More than 85% of honey was actually corn syrup and food coloring, a damn cheat you still see today — looking at you, KFC “honey sauce” — but at least it’s labeled.  Both the maple syrup and honey lies were unveiled by Dr. Harvey Wiley, chief chemist at the Department of Agriculture in the 1890’s.


Almost as soon as he got the job, Wiley petitioned the government to conduct similar experiments, only to be rebuffed by his bosses under pressure from food industry lobbyists.  If there was one kind of person I could get rid of…   Finally in 1902, Wiley was given funding and free reign to test the safety of various food preservatives.   His next step was to take on a dozen volunteers for a five-year series of experiments the media would come to dub “The Poison Squad Trials”.  While you might think finding volunteers to potentially ingest something harmful to the human body would be difficult, Wiley was actually inundated with requests from men wanting to join.  Women, naturally for the era, were not eligible.  Why would people be anxious to be slowly poisoned?  Wiley was offering a bit of pay, along with free lodging and prepared meals for a minimum of six months, with the person otherwise being able to go about their regular lives as they pleased.  I mean, I’d think about it.  All you had to do to get those perks was eat whatever was put in front of you…and agree not to sue him if things went pear-shaped.


The general method to figure out if the doses in common products were hazardous was to start with ultra low doses and slowly increase it over time, until the subjects exhibited adverse effects.  The first substance in the dock was borax, which was commonly used to preserve meat at the time.  The experiment hit a stumbling block early-doors when volunteers were unable to overcome borax’s strong metallic taste.  Wiley had to pivot to giving them the borax in a pill.  It took a few weeks, but the effects of the borax ingestion began to manifest, everything from headaches to depression, with symptoms worsening as the doses increased.  A few *months into the borax-eating, volunteers briefly went on strike because the symptoms had gotten so severe and Wiley cut the experiment short.  


The volunteers’ vital signs were carefully measured several times a day and they were forbidden from eating any outside food so as to not contaminate the findings.  Volunteers were rotated out after each substance was tested for the same reason.  They were also given a medical satchel containing various vials and containers for collecting urine and fecal samples.  On balance, the meals were prepared by a chef and served in a restaurant setting and the men were expected to dress properly for dinner.  This made for great press photos of what Wiley called “The Hygenic Table Trials,” but what everyone else called “The Poison Squad.”  Wiley saw the importance of press coverage and he would publish his monthly findings.  Wiley and the Poison Squad were not popular with food producers.  When efforts to block the release of his findings failed, various industry insiders took to attacking Wiley’s credibility and claiming he was out to hurt American businesses.  Wiley knew that if he was going to get politicians to take action, he would need the public putting pressure on them.  Now it was time for women to play their part.  Empowered suffragettes and mothers concerned with what they’d been feeding their children spearheaded the movement for what would become the 1906 Pure Food and Drug Act, aptly nicknamed The Wiley Act.  I suppose we do have to give some of the credit to Upton Sinclair, whose book The Jungle was supposed to shed light on the conditions of slaughterhouse and meat-packing plant workers, but instead horrified the public with what was really happening to their steaks and chops behind closed doors.  The less said about ground meat and sausages, the better.


This Wiley Act established the Food and Drug Administration and put in place rules requiring listing ingredients on labels so consumers could know, at least to some extent, what they were actually getting.  The idea at this point was not so much to regulate the industries directly, but rather increase transparency so the consumers could decide whether they wanted to drink something that used formaldehyde as a preservative, for example.  But the Act, as written, left an amazing amount of wiggle room, loopholes, and technicalities for companies to exploit, culminating in the infamous Elixir Sulfanilamide Incident.  You can read more about this in the YBOF book, in the section Unsungest Heroes.  TL:DR 107 people, most of them children, were killed when the bitter taste of a medicine was covered with the sweet taste of ethylene glycol, aka antifreeze.  While we’re being down-beat, there was one death in the Poison Squad, but the man’s family held no grudge against Wiley.  They understand the importance of what the volunteers were doing.  His mother referred to her late son as “a martyr to science.”  His death and the sickness of his comrades was not in vain.  Though the Poison Squad is little-known today, they were instrumental in the first significant step towards making sure food consumed in the U.S. is as safe as it is and why you can go to the store and know that your milk is milk, and not chalk water and brains.


And that’s…