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!