The Dose Makes the Poison

I recently stumbled across this quote by Paracelsus (ok, I knew it before, but not who originated it), and it fits well with the topics I frequent here on the blog. Food, cooking, chemistry, wild edibles – and their flip side, wild poisons. Snakes, spiders, centipedes… and sometimes wasps. Toxicology has been a long-time interest of mine, and being out of school doesn’t mean I am going to stop reading and learning on this and other topics, even if I don’t need them for work. I’m not letting my brain stay still and get rusty!

Anything can be a poison. Literally any substance can, taken in excess, kill you. Drink too much water? first, you get water intoxication, and then, death. There is some argument that eating too much food leads to morbid obesity, and that can kill, too. I’m not as sure I’d define it that way – there’s no direct biochemical tie between eating too much and death, there. Of course, if you stop eating and drinking and take only air, that’ll kill you, too. And then we get into carcinogens, which are substances that, once ingested or taken into the body in some other way, have the capacity to mutate your own cells until they become something malignant which proliferate out of control – and that’s what cancer is. So poison, then, is not always something that kills quickly. Some cancers grow so slowly they might be in the body for years before detection, and not cause death for years later. Some toxins affect one person, but not another. Our own immune system can freak out at an allergen, and kill us (within minutes, in rare cases). Some people – like my Dad – aren’t allergic to poison oak and ivy, while the rest of us avoid it like the plague.

Having settled that toxic substances are various and their affects on the human body even more varied, we next look at the dosage. Water, to begin with, is a necessary substance to most mammalian life, including humans. There is a mouse that can survive without ever drinking water (and, curiously, it passes dust for uric acid elimination) by consuming liquid in the foods it eats. It has simply amazing kidneys. Humans are not so equipped, and must drink from time to time. Water is an essential substance, but also a poison – if taken in too large an amount. Humans can consume arsenic, to name one particularly nasty heavy metal poison most of us are familiar with from murder mysteries, in small amounts. And have done so willingly over the course of history, in the name of medicine and beauty. Remember how I said any substance? Well, oxygen is also a toxic substance – oxidation is a powerfully cytotoxic process, killing cells and accelerating mutagenesis, which is one path that leads to cancer. So if you breathe, you die. If you don’t breathe, you die.

Now that you’re staring around you in horror wondering what’s trying to kill you, and knowing the answer is everything, take a deep breath. Relax. We’re all going to die – that’s another article, for another time – the question is simply ‘when?’ There are things you can do to hold death at bay, but quitting food, water, and air is a bad idea. Aside from out and out poisons like ricin, Pu239, and amanita mushrooms, people worry about some odd things they are convinced are killing them. The good news is, science studies stuff people worry about, and sometimes they even find answers. Not always, but there are some things you can stop worrying about now, unless you plan to eat a whole lot of, say, sodium benzoate.

Derek Lowe, one of my favorite chemist bloggers, wrote this up recently about the sensationalist commercials targeting sodium benzoate: “Somehow, turning fresh, pure benzoic acid into its sodium salt puts the Curse of the Vat onto it, and this evil stain can never be removed, as we all know. The first idiotic part of this, as the chemists are well aware, is that in foods that contain benzoic acid, a goodly fraction of it is already present as the benzoate anion. […] Benzoic acid is found (as a completely natural metabolite and intermediate) in a huge variety of foods, especially fruits and vegetables – berries are particularly high in it, but it’s also found in aromatic spices such as cinnamon and allspice. There’s not much in meat, but it is found in seafood, and in milk, particularly in fermented milk products such as completely natural, non-GMO yogurt made by people wearing unbleached hemp clothing and singing to each other about their feelings. OK, I’ll try to resist going off like that again (it’s difficult), but it’s certainly true that the bacterial metabolic pathways in fermented milk products like cheese and yogurt produce a good amount of benzoate.”

The problem, of course, with assuming that stuff like this is a legitimate danger, or paying too much attention to the stickers and tags warning that ‘according to California this product may cause cancer’, is that people either stop paying any attention at all to them, or they assume that they are valid. That latter conclusion is a problem. Studies that show a substance causes cancer in a rat or mouse are usually based on data that involved feeding (or rubbing on them, or injecting, or…) an extremely high dosage versus body size. So if a gram is fed to a 1 kg rat, say, you’d have to eat more like 100 grams. Pick up the nearest food product to you and read off how much it weighs in grams – most if not all labels will have this information. We Americans are married to the imperial system, but science likes things easier, so we’re all SI (Systeme Internationale) and you’ll have to be patient with me. Now, imagine eating that much of whatever carcinogenic substance you’re worried about. Daily. For a prolonged period of time. There are very few substances that will cause cancer in small enough doses for you to be worried about it in normal day-to-day life.

Animal testing, sometimes called in vivo testing, is one of the primary ways science can determine just how toxic a substance is. These model organisms are chosen for how similar they are to human systems, but that similarity is not always as close as perhaps it should be. Additionally, in order to give a living thing cancer, you have to use what is called the Maximum Tolerated Dose (MTD). The idea here is to kill healthy cells off, forcing nearby cells to reproduce to fill in the gap (so to speak. You can actually think of this as a parallel to stabbing them with a knife, repeatedly, and waiting for them to heal again. And that too can lead to cancer). During cell division, the DNA is vulnerable to mutations, and eventually, with enough divisions, there will be mutations. With enough mutations (it’s not just one, it’s usually at minimum two or three) the cells start to go insane, and divide and reproduce out of control. Voila! You can cause cancer. The alternative to this, by the way, is known as the Ames test when it’s done in a petrie dish with specially mutated bacteria, and it’s a fascinating process which can be very helpful in things like drug development and testing.

So. We gave a mouse cancer. What now? Well, as you can see this is not a very helpful process when we compare it to a human. You’re hardly likely to eat/inject/roll around in that much of whatever substance was being tested. I’m not saying that nothing is a carcinogen. I’m saying that fewer things are lethal at normal daily dosages than you’ve been lead to believe.

But what about chemicals? nasty synthetic stuff, like pesticides! Dr. Bruce Ames (of the above Ames test) says this: About 99.99% of all pesticides in the human diet are natural pesticides from All plants produce toxins to protect themselves against fungi, insects, and animal predators such as man. Tens of thousands of these natural pesticides have been discovered, and every species of plant contains its own set of different toxins, usually a few dozen. When plants are stressed or damaged (e.g., during a pest attack), they increase the levels of natural pesticides manyfold, occasionally to levels that are acutely toxic to humans.”  he goes on to point out that when tests are conducted, the levels of natural pesticides are usually measured in parts per million, while synthetic pesticides are measured in parts per billion. That is a rather significant difference, if it’s not clear. “Thus, it is probable that almost every plant product in the supermarket contains natural carcinogens.”

There has been growing concern – I might even term it hysteria – that man-made chemicals contaminate our daily lives and lead to an upsurgence in diseases, especially cancer. “For the first time in the history of the world, every human being is now subjected to contact with dangerous chemicals, from the moment of conception until death” (Rachel Carson: Silent Spring, 1962). “We find this assumption flawed for several reasons” (Dr. Bruce Ames, Misconceptions on Pollution and the Causes of Cancer, 1990).

We consume poisons every day, from our first cup of coffee to our cabbage rolls, to the drugs our doctor prescribed to cure what ails us. The challenge lies in determining how much of what will harm us. Testing in vitro is not at all analogous to what actually happens in living cells, because we have detoxifying processes, and repair processes, and proof-reading for our DNA and RNA. Studies that show caffeine is dangerous to cells in a petrie dish are not the same as that equivalent amount of caffeine causing damage in the human body. Bruce Ames’ paper on the 8 most common misconceptions about cancer-causing agents is a must-read, in my opinion, and a goodly amount of what I’ve talked about here he covers in much more detail. Did you know that alcohol and broccoli are both more toxic (using a certain ruler to measure) than dioxin?

And now, I’m off to sip a nice hot cup of steaming poisons. I shall raise a glass of that toxic substance, alcohol, to you, my readers, before I ingest some tasty pastry with deadly sugar. And probably natural pesticides in my berry pie. Bon Appetit!


19 responses to “The Dose Makes the Poison”

  1. Trudy W. Schuett Avatar
    Trudy W. Schuett

    Excellent! I’ll be printing this out to share with a couple of family members. I’ve been telling them essentially the same thing for years w/o success, though your approach is much, much better. Thank you!

    1. hopefully it helps – I think I’ll do a follow-up post about why we persistently (as a culture) fall into these traps. And that ties into JRR Tolkein, among other people.

      1. Please! I’d really like to read that one.

  2. “There is a mouse that can survive without ever drinking water (and, curiously, it passes dust for uric acid elimination) by consuming liquid in the foods it eats.” Likewise, for the most part, the common Mediterranean tortoise (testudo graeca terrestris), of which we used to have several in our garden — if adequate greens are available for them to eat, they rarely drink at all, and often they excrete what seems mostly solid urea instead of urinating.

    1. Birds do something similar as well, with commingled urea and fecal matter in the cloaca excreted in a near-solid state. It’s really nifty to get into looking at how different systems for handling wastes work – from primitive invertebrates to these tortoises and mice. Sigh – science, where you can wax enthusiastic over poop and pee. Reminds me of potty training toddlers!

  3. Larry Patterson Avatar
    Larry Patterson

    I want to share this on FB in hopes my friends of the 60s will stop the anti-vax and other historiae, or at least take a breath and calm down. Our problem is we thought we knew everything then, and too many still know everything.

    1. Please do share. Dr. Ames’ paper was written 27 years ago, but you wouldn’t know that from the way mass media gets hysterical over ‘chemicals’ on a regular basis.

      Science is never settled. We just don’t know everything, and if we stop questioning we are no longer proceeding with science.

      1. Larry Patterson Avatar
        Larry Patterson

        That’s the problem with my generation. Modesty means recognizing your own limitations. But we thought we didn’t have any limitations. Even to the point of claiming that everyone who doesn’t believe in the ridiculous notion of “settled science” is a “denier,” i.e. a heretic.

        1. Which is in and of itself a limit. So they are setting up limitations?

  4. Javahead Avatar

    There were a couple of death-by-water-poisoning cases here in California about a decade back.

    Some radio-station hosts came up with a contest – “Would you hold your wee for Wii?”

    Participants would drink an 8 oz bottle of water, wait 10 minutes, drink another . . . And the last one to urinate won.

    Several people (including at least one RN) called the station before the contest to warn them of the possible dangers, but were ignored. The winner managed to drink about 30 bottles over the course of 5 hours . . . and died of water intoxication. The station ended up paying her family a settlement, and firing about 10 people.

    What made it even stupider is that just a couple of years earlier a local college student died a similar (and well publicized) death during fraternity hazing.

    1. You can also die of your bladder bursting (can’t think of the name of the historical figure who was said to have done this).

      1. The likely cause of death of the astronomer Tycho Brahe is considered to be a burst bladder.

        1. Thank you, I was drawing a blank on the name!

  5. […] I wrote about the myths surrounding chemicals, cancer, and foods, and how it has come to a crescendo in the recent decades. A near hysteria surrounds the idea that […]

  6. Cedar, A distant but dear Facebook acquaintance just posted a link to what I think is most likely a scare story:

    And I wondered what you know or would say to this particular article: is this really legitimate, or, if not, from your background, what can you see that is an obvious sign of a scare vs. real science?

    1. Since I can refute this with, of all sources, a Mother Jones article…

      There is a LOT of hysteria and false information out there about glyphosphate, the active ingredient in RoundUp, among other things. Scientific studies, on the other hand, don’t reflect the same dangers. Here’s the link to the in-depth Reuters expose on that flawed paper.

      1. Cedar, thank you for that quick reference material. I posted both links to the dear lady’s post with comments cautioning belief in such scare stories. Alas, her story has the better narrative about evil money-grubbing corporations, instead of legitimate businessmen earning a living making the world a better, healthier and richer place for us all. We will see if she accepts the truth, or the “right narrative”. But at least I tried (again, with your gracious and capable help).

        Keep up these interesting and thoughtful posts.

        1. I shall endeavour to continue. I have been able to take more time for blogging in depth, and I find I’m much happier with these type of articles than simply generating filler. Although I will always do food and art posts too!

          1. Hey, I think these articles and the food and art posts are equally “in depth blogging”, just depths of different areas. Personally, I like the eclectic mix. Seeing you post about so many of your passions is enjoyable, refreshing, and sometimes a positive challenge for us all. Keep following whatever muse selects these wonderful blog topics!