 Okay, everybody please take a seat. I'm very pleased to introduce George Diggs, PhD. He is an evolutionary biologist and botanist who has taught for more than 30 years at Austin College in Sherman, Texas. He last year published a book called The Hunter Gatherer Within Health and the Natural Human Diet and he will be signing the book at four o'clock, I believe. Here he goes. Hello. Thanks. So I'm going to talk about some of the plant food toxins that many of us have heard about and try to put them in an evolutionary context. So obviously the first couple of slides here in one minute, just the background. Creatures defend themselves in very different ways. So animals obviously can flee but plants are helpless. This is a very vicious predator here eating these innocent plants and plants though, however, are not so innocent. They defend themselves in a variety of ways. I'll just mention two or three before I get to the chemical ones just very briefly. Physical defense we all know about. It's not very complex. Animal guard defense is quite interesting. There are a lot of plants that actually hire ants using various types of rewards, different kinds of food, shelter and these ants in fact defend the plants vigorously from their predators, actually attack things that would try to eat the plants. And there's some fascinating visual defenses as well. The passion flower, for example, has evolved egg mimics. These are these little dots you can see on the surface of the leaves. And they, we think mimic the eggs of certain kinds of butterflies which choose these plants visually and this prevents then the butterflies from laying the eggs because there's already eggs there and there wouldn't be enough food for the new eggs to hatch and turn to larvae and eat them. But chemical defense is what I wanna focus on and there's a wide variety of toxic plants that affect many kinds of creatures. Plants are really biochemical factories. They're not simple things. My students sometimes say that act like plants are so much simpler than we are. Well, plants have many more genes in many cases than we do. Rice, for example, has at least 32,000 genes. Humans have somewhere around 23,000 wheat has even more. And in the last few decades, there's been a tremendous increase in our understanding particularly about chemical defense and how plants are able to protect themselves against herbivores and pathogens. It's not just things that would, large things that would eat them but it's also various kinds of bacteria and fungi that have pathogenic attacks. Now, I've spent my career doing a lot of research in Texas, some of the plants there and in a couple of my books in the past, these are some of the conditions that animals face when eating certain plants. Most of these I don't think any of us want. The blind staggers, I particularly don't want the slobbers, big head, limp neck, crazy cow syndrome. Now, this doesn't usually happen in wild animals. This usually happens in domestic livestock when they get trapped in a pasture and they're so desperate they eat things that they would not normally eat. Now, there are various ways you can divide up chemical defenses and plants. You can do it by the chemical structure. You can do it functionally. I think this is a pretty effective way to do it functionally. So I'll mention today three categories at some length and I'll just talk about this one first briefly. But toxins are things that actually damage the eater in some way. Hormo disruptors, I think that's pretty obvious. Digestibility reducers, this makes the food that's eaten indigestible, it makes it basically not worth eating. So let me just give the 30 second version on semi-ochemicals to show you the sophistication of some of the plant defenses and then I'll actually get to the toxins and other things. So the semi-ochemicals are something that we've now known about for a number of years but I find them particularly interesting. These are chemical signals to attract the enemies of your enemies. It's like calling in the cavalry. So let's take, for example, a caterpillar that's being damaged, sorry, a plant that's being damaged by a caterpillar. So this plant maybe is being damaged by a caterpillar and that plant then is sending out signals, volatile molecules that disperse in the environment and attract parasitic wasp which come in and then attack those caterpillars. So this is an indirect sort of defense, pretty sophisticated way to do it and so this, for example, is another situation. Wasp came in, laid eggs and this caterpillar is literally eaten from the inside out. They may still be moving but they're the living dead at this point. So semi-ochemicals are pretty sophisticated ways of plant defense. I don't know of any examples though where that has an effect on us. There are many defenses though that do affect us in a variety of ways. So toxins, as I say, are defenses that damage the eater and I think of these as things that either disrupt the metabolism or the structure and I'll give examples of both of these. And there are many different kinds of toxins. Some of these affect the nervous system, some stop respiration, some inhibit digestive enzymes, some damage the gut lining. So there's a host of different ways and all of these can have effects on us. So just to give you one example of a pretty poisonous plant, one of the most poisonous plants in the northern hemisphere and one that's very common where I'm at and it also comes over here to the west coast, water hemlock or cowbane. We now understand how that's so poisonous. It disrupts the central nervous system. Technically it's a GABA receptor antagonist and it results in seizures and coma and death in minutes. This is not something you wanna eat. And here's a little quote I wrote years ago. It's virulently poisonous. A single bite is reported to be sufficient to kill a human. Children that have even been poisoned by whistles made from the stem. So this is a very poisonous plant. Dr. Noelle said earlier this morning, everything that's natural is not necessarily good, necessarily good. I couldn't emphasize that more. And this isn't really so strange though when you think about there are certain pills that a small amount can do very potent things to people. But this plant is widespread and it's quite toxic. Fortunately, most people are never exposed to it. Now the way I'd like to develop my ideas, I wanna give examples of chemical defense in nature and then follow that with a similar example of chemical defenses in our food. So show this makes sense in the evolutionary context. Plants have evolved this kind of thing to do it to various creatures and we are sometimes the unfortunate beneficiaries of their defenses. Very few of these are probably none of them evolved actually to defend against our species and in many cases not even against mammals. But that doesn't mean that they don't have harmful effects on us. And that's because at the cellular level we are remarkably similar to insects and all other animals. And many of these same compounds have similar effects against things even as far from us as fungi. In fact, some of the things that harm us probably evolved to defend against not even animals. So let's think first about digestive enzyme inhibitors. So these are things that inhibit the enzymes that we make to digest our food. And one example of this is a protease inhibitor. These inhibit our ability to digest proteins. Now if your herbivore in your eating plants, if you're an insect and you can't digest proteins that means you can't get essential amino acids and that's going to compromise your nutrition. Now when you put this in the context of natural selection, these things don't usually kill the herbivore directly. So it's not like the herbivore would eat the plant and then the creature die. And then some people say, well, why does that matter? Well it matters because herbivores that choose other plants survive and reproduce better. And so plants have evolved ways to make themselves less likely targets. And so herbivores will then eat other plants and they're the ones that survive and reproduce and then their offspring tend to select those other plants as well. So let's look at one particular protease inhibitor, the one in soybeans. And we know that has an effect on the digestion of many insects. This has been studied in many, many insects, things like beetles, tobacco hornworm, corn earworm, many, many. And we see similar digestive enzyme inhibitors and in many seeds. And by the way, the soybean protease inhibitors also affect lamb animals. And how about humans? And at what dosage? Dosage is a very big thing. We can often stand small dosages of many things, but if we up the dosage, so if somebody's eating huge amounts of soy that is not properly processed, then it wouldn't be surprising that the protease inhibitors might be having some effect. Wheat protease inhibitors are I think maybe more of an issue for many people because they've now been shown to be strong triggers for an innate immune response in cells both from celiac and non-celiac patients. So this is not something that's, this is totally different from gluten. This is not related to celiac because it apparently can affect cells from a wide variety of patients. And it looks like it's fueling inflammation. There's a paper published about a year and a half ago, wheat amylase trips and inhibitors drive intestinal inflammation via activation of toll-like receptor four. So we're now at the mechanistic level understanding how this is happening. Could this be involved in what we call non-celiac gluten sensitivity? Might it be not actually gluten in a case like this, but some other component of wheat because wheat has multiple defensive compounds. It's something that hopefully in the future we'll know more about, but I find it pretty interesting. And I wanna emphasize, this is different from gluten. Gluten is a storage protein and obviously it can cause very serious problems. I'm really not gonna talk about it today. I think this audience is sophisticated and probably is very familiar with this kind of situation. But I will mention one thing. We do know that storage proteins in other seeds and in other plant organs are also known to function in defense. So just because a protein, its main function is storage does not mean it can't also function in defense because many things about organisms have more than one function. Natural selection has driven to often one compound having multiple functions. So I'm gonna focus on the other plant defenses. I'm not really gonna say anything else about gluten. Now, what I was just telling you about would affect the metabolism. It affects the digestion enzymes. This is something different. This is where the digestive system is actually physically damaged. So this was a paper published a number of years ago. The title is insect feeding. Mobilizes a new plant defense protease that disrupts the paratroopic matrix of caterpillars. What a mouthful. That just means it screwed up the digestive system of the caterpillar. So this is a popular press translation of that. The title, bitten plants deploy gut rotting enzyme. So it actually damages the gut of the animal and they do not grow properly. So in this article it said it leaves the gut lining in tatters. Well that's pretty dramatic when you think about it. You wouldn't wanna be that poor insect, right? I don't think anything we're gonna get served for lunch today will leave our gut lining in tatters. Certainly hope not. So it's almost like molecular scissors if something is a gut rotting enzyme. So this is what we see in a case in insects. But how about other things that damage the gut? For example, plant lectins. Now lectins are a type of defense protein that bind to sugars and our gut cells have sugar molecules attached on the surface and so some of these lectins can actually bind to the lining of our intestinal epithelium, our gut lining. And we've all heard of lectins but what did they evolve to do? Probably not to defend against us. So it turns out that lectins are very ancient molecules. They're in animals, they're in plants, but they probably did not evolve to defend against mammals. And it turns out that plant lectins are probably protection against pathogens, things like fungi and insects. So let me give you a specific example in the animal world and then we'll turn to a human example. So wheat germaglutinin. We've all probably heard of this, WGA. It turns out it inhibits the growth of fungi and it also binds to bacterial cells. This probably is a pathogen defense. And here's a paper from years ago, the inhibition of fungal growth by wheat germaglutinin. So may have it well evolved as a pathogen defense, maybe also as an insect defense, because wheat germaglutinin is so potent against insects that biochemical, biotech companies have now genetically engineered crop plants to express wheat germaglutinin. So you can now get corn with wheat germaglutinin, you can now get tomatoes with wheat germaglutinin. Goodness, I hope we're not gonna get any of those. But we know this is very potent stuff against insects. Enough so they're trying to genetically engineer their crops. We know also that wheat germaglutinin damages the gut of rats and enters the systemic circulation. And we know that it affects human gut epithelial cells, leaky gut. So this is, we've known this, but people could, and we know it causes inflammation. This is a paper from about a little over a year ago and this focused on one of the focuses were wheat germaglutinin. So we know that it can do these things, but people will say it's temperature sensitive. And indeed it is. If you cook things, if you, at the right temperature for long enough, you can break down much of the wheat germaglutinin. But let's think about in our society, do we actually eat things that have the wheat germaglutinin completely knocked out or even mostly knocked out? I don't think so. We know from research, I've got a reference here you can look in that in some cereals there's wheat germaglutinin still there. So depending on the processing, how about other processed foods? How much wheat germaglutinin is there? How about poorly cooked or uncooked wheat products? Pasta that's not cooked properly. Kids eating cookie dough. And how about wheat germ which is often eaten raw? So it turns out wheat eaters are probably getting significant amounts of wheat germaglutinin and we know that this has biological activity. In fact you can recover it from fecal, you can recover active, biologically active wheat germaglutinin from fecal samples. So ironically though, this wheat germaglutinin damage is probably a quirk of our similarity at the cellular level. It did not evolve as a defense against humans. That's pretty clear. How about cyanogenic glycosides? It's a big word. This just, these are just compounds that release cyanide. So I think all of us have heard about cyanide. It blocks respiration. It's a quick way to die if you're exposed to large amounts of cyanide. Entomologists use it to kill insects because it'll kill the insects quite quickly. And their cyanogenic glycosides are in a number of plants, things like cherries and peaches in the pits. And there's good evidence that this is a defense against herbivores. It's in a lot of plants. We know it in over 2,500 plant species and this stuff is released upon tissue damage. So it's in an inactive form and when tissue is damaged by something eating it, then that causes the cyanide to be released. And it's in a number of things. Bitter almonds is one that has a lot of cyanide. Almonds, very small amounts. Cherries, most cherries, the fruits, tiny amounts. Cherry foliage is significant, as I'll mention. It's known in a number of other things. Sorghum is a grass and there's a lot in the leaves in some cases. The only case where we're probably getting very much inhuman food is from cassava or yucca. That's the one I'm most concerned about and I'll mention it to you. But let's look at livestock first. Sorghum, it's a grass. Some people may call it one of the related grasses, sweet-sue or pseudangrass. But ranchers and farmers have to be quite careful not to let their cattle graze on these grasses at certain times because it can be very serious. Likewise, cherries, wilted cherry leaves. I grew up on a farm in Virginia and we were quite careful if a branch of a cherry tree fell in a pasture, you had to get those wilted cherry leaves out because that could be problematic for your cattle. So we know this can have effects on mammals and the onset of symptoms can be quite rapid and you can have things like weakness and incoordination, seizures and rarely even death. So the cyanogenic glycosides are not trivial. Now how about, is there any real worry for most of us? Probably not because we're not gonna be eating huge amounts of this, particularly in an unprocessed in an inappropriate form and also many of the cultivated varieties are fairly low in cyanogenic glycosides. This plant, if anybody's ever been into a third world country in the tropics, you've eaten probably a good bit of cassava or yucca. I certainly have and it's often what's called sweet cassava. It has fewer of the toxins but people who are in areas with problems with herbivores, things eating their crops, they often grow the bitter cassava which has a lot of cyanide and then it has to be processed properly or there are problems. So cassava is not trivial. It's the third most important source of calories in the tropics after corn and rice and it's the primary source of calories for almost 500 million people. So there are a lot of people eating cassava. Well, how about toxicity? Well, long-term consumption of cassava, particularly if it's improperly processed or if the person is malnourished and this is the case, particularly in some parts of tropical Africa, this can result in very serious thyroid and neurological problems, very serious and overall this and other cyanogenic glycoside plants are probably not a problem for people but it has been quite problematic for some people causing a lifelong disability. So let's switch gears and look at another one that I find particularly fascinating and that's photosensitizers. Now, why am I tempting you with a margarita? Here in the middle of the day before lunch. Well, photosensitizers are toxins that make animals sensitive to light and these are important in plant defense. So it makes them sensitive to light. One example of this is celery. I'll tell you a little bit more about it. Another example is wild parsnip. These are both in the carrot family. I'm gonna mention two families, the carrot and the citrus family that are well-known for photosensitizers. So the carrot family, the citrus family, there are a number of others and these photosensitizers are technically called ferrano-cumerins. These are phenolic, that just means polyphenolic, multiple ring compounds that become light activated. So when light hits them, it changes them chemically and they become activated and they can then cross-link with DNA and they can also modify proteins. So they actually damage DNA and proteins in the presence of light. This is an example of one. This is xanthotoxin. You can see the multiple rings and that rings are important because they're involved in the light activation. So here's a title of a paper from another number of years ago. The toxicity of a ferrano-cumerin to armyworms. So these protect the plants by actually damaging the animals. So an animal comes and eats the plant and then light hits that animal and the animal is severely injured. This can be quite a good plant defense. Now, it can also affect mammals. So this is a problem for livestock in some areas. Sheep, cattle, through either contact with the plant or through eating it. If they eat it, then these compounds will move through the blood and where the skin is not well covered with hair, any exposed area, then the animal gets a reaction. So this is a poor sheep that has had a photosensitive reaction. It's a photodermatitis and its ears and face are not good. There can be blistering lesions, swelling of the head. The head will actually get large because it swells, particularly in unpigmented or exposed areas. Utters, for example, are another place that don't have a lot of hair. So animals can really suffer from this. Now, there are some insects like this nice black swallowtail, which is native where I'm at. These black swallowtails, and this is its caterpillar, these guys actually preferentially seek out plants that make these. So they eat these poisonous things, okay? So they're very unusual. They choose the plants. And this is where the animals have evolved in response to the plants. So this whole, this is not just a one-way thing, there's all this co-evolution going on. As one evolves, the other evolves. It's like an arms race. And so these black swallowtails have actually evolved a way to break down these toxins. So they've evolved special cytochrome P450 detox enzymes. Now we all have P450 detox enzymes in our livers. We've heard of phase one and phase two liver detox. These P450s are involved in the first step, phase one of our liver detox. And so these butterflies can thus eat the plants, and this is like they've got their own specially guarded food supply. And so once they've broken through that defense, that's really advantageous for them. And so they seek out these compounds, seek out the plants with these compounds. Now let's put this in the human context. Some of you have probably heard on the news that grapefruit can be a problem with certain medications. We now know of about 80 prescription drug grapefruit interactions. One of the best examples of this is statins. So some people can have pretty serious reactions. And we now understand how this works. So it turns out that grapefruit has some of these furanocumerins. Now they're not the ones here are not gonna be causing photosensitization, but they're still toxic and have to be broken down. And so we have P450s in our liver that are trying to break down these grapefruit toxins. But those same P450s are the ones that have to metabolize the drugs. And so if the P450s are busy with furanocumerins, they can't detoxify the drugs. And so you get higher than normal levels of the drugs in the bloodstream. So we now understand that you're here these molecules that have evolved to protect plants against predators. And they're affecting us when we are taking certain drugs. Celery is also kind of fun. It's a known occupational risk for celery handlers and celery pickers. People who are exposed to lots of celery, they get what's called celery dermatitis. If they go out in the sun after being exposed to lots of celery, then they get these reactions. And this is particularly if the celery has been infected with a fungus because the plant's response is to make more of these toxins. So the plant is not necessarily making lots and lots of any particular toxin at a given time. It's making some, but it'll make more if it's being damaged by some type of pathogen. Now, the reason I showed a margarita is because lime juice is a well-known cause of photodermatitis. So if you squeeze limes and then go out in the sun, you're at pretty serious risk. And this can actually be a horrifying manifestation. Your hands will swell up, they'll be blistered. It's just, and people who don't understand what's happening, they go to the physician. Often dermatologists know about this, but often other physicians don't recognize it. They don't know what's happened, but the people's hand, I've seen this, it's just horrifying. Here, for example, this made the news last year, national news, limes blame for girls' second degree burns. She had, I don't know if it's large enough for you to see, but she's got pretty serious burns from lime exposure. So again, these plants did not evolve this to do to us, but they evolved it to do to their things that would hurt them. Now, these liver detox enzymes detox many different plant toxins. And one of these that I think is kind of a fun example that can put this in a little perspective is that caffeine and chocolate are much more toxic to dogs than to humans. Some of you have heard about this, you can't give your dogs chocolate. And that's because they have slightly different P450s, dogs have slightly different P450 enzymes, detox enzymes, and they can't break down very well what are called Zant Themes and both caffeine and theobromine, the compounded chocolate are Zant Themes. And so dogs are sensitive to this. They're so sensitive in fact that here was a paper from a number of years ago, the evaluation of cocoa and coffee-derived methyl-Zant Themes as toxicants for the control of pest coyotes. So we're actually testing this stuff to use as poisons on coyotes. So they're pretty toxic to canines. A fatal dose is in the range of 100 to 250 milligrams per kilogram of body weight, literally death by chocolate. Wouldn't be such a bad way to go, I guess. Now, let's put this in a perspective, what does this mean? How much chocolate could you give a dog? By the way, here's some of the symptoms. Vomiting, staggering, agitation, seizures, in some cases even death, it affects the central nervous system. An 18-pound dog can be poisoned by consuming two ounces of baking chocolate. So two ounces is not that much. Now, milk could take a lot of milk chocolate to kill a dog, because there's not much of theobromine in it. But nonetheless, this is pretty toxic to animals. Now, why did I mention this? Well, clearly different species have somewhat different P450s, right? Thank you. But people can have different P450s. So I might have a P450 with a different activity level than Mark would, okay? And if I take a certain amount of drug, or if I take a certain amount of coffee, Mark's a little different, it may have a radically different effect on him than it does me. So some of these individual differences are probably pretty significant. It's not surprising we have different tolerances for different types of materials. Okay, let's look at hormone disruptors. This is a different group of plant defense chemicals. And obviously these are things that mimic the hormones of herbivores, and we know them from many plants. This is just an example. So there's a particular subgroup of plant hormones that affect metamorphosis in insects. And these are called phytoic dysones. Here is a poor pupa, an insect pupa, with three heads. So this creature, unfortunate creature, ate some of a particular plant. It's called a bugleweed that has these phytoic dysones. And as a result, its whole developmental pattern was thrown out of kilter. Now if we think about this, this is a gross physical manifestation, but it wouldn't have to be this gross physical manifestation to have profound influences, would it? But this is just, I use this because it was such a dramatic example. How about hormone mimics in our own food? Well let's look at the phytoestrogens, the compounds that mimic female hormones in soy, as an example in our food. So soy beans make these compounds called isoflavones. And these are plant defense phytoestrogens. And they're excellent fungicides. So this is a soybean leaf with some rust. It's a type of fungus. And so they probably evolved to protect the plant against fungi and possibly insects. And we know that plants under attack make more. So this is what you'd expect of a defense chemical, isn't it? The plants being attacked make sense for the plant to up-regulate its production. And we can see that this is one of the phytoestrogens from soy and this is human estrogen. And you can see there are similarities in the molecule and it's not surprising that there may be some, our body may confuse this at the receptor level. Now, so these are phytoestrogens. We can go to a health food store and we can find books like this. This is by an MD. The soy is recommended for menopausal women. Here's a supplement that talks about it. Okay, so this is one of these things that it really makes me think humans can compartmentalize our minds so remarkably. We can say, okay, postmenopausal women take soy and then we give children this as their sole nutrition in some cases, soy formula. Which to me, I just think about, I think, wow. And when are we most sensitive to hormonal influences when we're very young? Now, some people would say, well, Asians eat a lot of soy. Well, it's not really that simple. They usually don't eat soy foods in large quantities unless forced to do so by famine or poverty. It's mainly as condiments in flavoring, not meat replacements. And then they also eat it in traditional fermented forms, which can reduce some of the toxins. So, and we know that these kinds of plant phytoestrogens can have profound effects on mammals. We've known since the 40s that they can cause serious reproductive problems in sheep. This is very well known. And we know it can cause problems for many other animals. So what's it doing in humans? How sensitive are humans to this? Well, it's not clear. But there are certainly a number of studies that raise red flags. For example, a study from 2008, Soy Causes of Reduction in Sperm Quality in Men. A study from a number of years before that, it causes changes in the sex hormone ratios in people. And a study that came out in 2010 raises real concerns about children. How much research has been done on this? How much do we need? But it certainly is something that we should be concerned about, I think. We do know that some research shows that urine levels of these isoflavones are 500 times higher in infants-fed soy formula. So we know that a lot of it is being metabolized and going through the body and can potentially be having effects. So I would say, why do it? Certainly there can be children who are lactose intolerant, but there have to be, it would seem, to be other alternatives that could be figured out. Now, one other category I'll mention just very quickly, and I won't spend much time on this, is kind of a fun one is digestibility reducers. These are things that, and these are not proteins, these are things like what we call tannins that actually make proteins indigestible. So if we had to get nutrition from leather shoes or belts, we couldn't do it because those proteins in there have been bound up with tannins, and that's what the tanning process does in Mexico, so those proteins can never be used. And they come from certain plants. These are large multi-ring chemicals, and we know they have strong negative effects on insects. How about other animals? It's kind of interesting. This, they're well known, tannins are well known to cause problems in animals. So this is from the Angus beef bulletin, not one of my usual references. But this talks about acorn poisoning in cattle. If cattle are trapped in an area and they have to eat acorns, you can poison a cow with too many acorns. They can stand to break down some, they cannot stand to break down huge amounts. Native Americans in some places would use acorns at certain times of the year, but they carefully leached tannins out of the acorns. The Native Americans who use these as a significant part of their diet. So these digestibility reducers. How about in humans now? Well, we know that tannins can cause kidney and liver damage in very large amounts. They can cause poisoning in humans and animals. But the good news is, problems are unlikely for most modern humans from the food and drink. We get some in wine, we get some in chocolate. We have the ability to detoxify some. And if we are eating a mixed diet, we're not getting huge amounts, and so they're probably not a problem for most of us unless there's some compromised metabolic pathway. But it's all about dosage. Native Americans were careful to leach out the tannins. Now I want to kind of wrap up. My last example is with a fern and I spent a good bit of time in the last several years doing research on ferns. And this is bracken fern. This is a very common fern in Texas. And also, it or a close relative is worldwide. It's one of the most widespread plants on the planet. And I'm using this example to show you the complexity of chemical defense, the multi-layer approach that some of these plants have evolved. So this thing has an enzyme that causes a fatal vitamin B deficiency in livestock if they eat too much. It has a toxin that's known to be mutagenic and carcinogenic. It has a cyanide producing toxin and it has a hormone mimic that disrupts insect metamorphosis. You would think this is not what you're gonna choose to snack on, right? But unfortunately, people do eat bracken fern fiddleheads. And in Japan and Brazil, where this is done, there's a close association between bracken consumption and cancers of the upper elementary tract. And we know that this toxin can cause DNA damage. So, but this is a long-term effect. How many other things do we eat where we don't see the long-term effect? It could be years before this had some effect. So, summary, the problems caused by the consumption of some plants, particularly in large amounts, is not at all surprising in the evolutionary context. Plants do fight or bite back sometimes and beware of what you eat. Plants give us a lot of good things, but they're not necessarily our friends. Thank you very much. Okay. We are technically at the end of our slot here, but I'd love to give an opportunity for some questions. If you have to go, please go ahead. But let's go ahead and take some questions. I think there's one here. Thank you. So, are you saying that I shouldn't eat carrots and celery, or are you saying that I shouldn't eat large amounts of carrots and celery? I guess I'm saying I wouldn't base my diet on any one plant. So, that's where we get in trouble. I eat good number of carrots, and I eat celery, and I enjoy it, but I wouldn't eat, you know, celery three meals a day. So, yeah, because our bodies can detoxify a lot of stuff, and it actually may help us through hormesis to detoxify some things. Yeah. So, and then I have another question, and that is about fungi. I have this craving. I eat so many raw mushrooms. I don't know if that's a good thing or a bad thing. Do fungi have the same defenses plants do? Absolutely. In fact, I've been involved in trying to help and fungal poisoning cases. I wouldn't advise eating any wild fungus, unless I know exactly what I was eating, and even some cultivated fungi have some pretty potent toxins. So, I would look into it and choose. Some fungi are great. Some are not so great. It's too complex to talk about here. I can talk to you a little bit more later afterwards. Are you aware of any toxins in garlic or anything from the garlic family? They certainly have toxins. I know that if you feed certain livestock, there were some examples, as I recall, from famine during World War II, where they were trying to keep some livestock alive feeding them large amounts. You can, with large amounts, poison creatures. So, there are defense chemicals there. And some of those defense chemicals may be good for us in moderate quantities, but like anything else, if you eat huge amounts. So, I would say yes, but I've never heard of any problem in humans with the amounts we eat. Did you have any thoughts on tubers and other below ground vegetables and peeling them before eating them? How does that help, or does it? You know, it's a great question. We know that in some tubers, there are more defense chemicals around the outside. So, that turns out to be the case with cassava, yuca. So, out towards the edges, higher levels of chemicals. If you think about potatoes or something, there's a higher level of some of the alkaloids out at the skin. Now, again, I would say it's probably a dosage effect, how much you're being exposed to. Knowing that most plants seem to have something that can affect us, in terms of preparation, in terms of eating them, is it just safer to cook most things to a certain level? Is there a certain method of cooking? I don't know of any research that's looked into that. I think that, you know, I've been talking about some of the toxicity. There are obviously a lot of benefits that plant compounds give for us. And so, when we cook them, we change what we're getting. So, we may reduce some toxins, but we may remove some things that might be helpful to us. So, I think you'd probably have to look almost on a plant by plant basis, and you'd also have to look at what component of your diet. So, if you think about hunter-gatherers, they were not eating over long periods of time huge amounts of any one thing. They had a mixed diet, and they're body, you know, we have all kinds of different P450s, and we can break down all kinds of toxins in that in other ways. And so, I would say a mixed, from the standpoint of what we see in animals, a mixed diet would make sense. I don't know of any that are available in the, you know, standard testing system. There might be, but I don't know of any. Not sure if my question is a question, but I'll ask it anyway. I saw that you had a koala bear eating a eucalyptus at one of your first pictures, and I believe they have a very tragic life where it's the only thing they can eat, but also, they find it very unpleasant, and it makes them grumpy. But it's the only thing they can eat. So, I was wondering if there's any parallels with us. I've actually been up close with koalas. I've not heard it makes them grumpy. They've evolved to be able to detoxify those eucalyptus leaves very effectively, and when you are close to one, they literally reek of the eucalyptus toxins. So, I can't address it. The BT toxin in GMO plants, I know it's not naturally a plant toxin, but now it is. Is it true that it has no effect on mammals? I cannot answer that. I don't know. I've not looked into BT. I've used it in my organic garden, but I've not looked into it how it affects us. Quick comment. I did the book, The Whole Soy Story, so very familiar. Oh, wonderful. I'm delighted to have you here. Thank you. Just wanted to comment quickly that besides the isoflavins in soybeans, there's the chumestins in other healthy things like alfalfa sprouts and clover, and lignins and flax oil, so let's not overdose on these things. And we're seeing a lot of people having spinach salads every day and developing oxalate problems. Absolutely. Another defense with oxalates. So people switch from, say, McDonald's burgers to spinach salads to get healthy, and they develop kidney stones and other agony. That's a great thing. I'm really glad you mentioned that. I had a student a number of years ago who for some reason ate spinach every day, and she was a 19 or 20-year-old college student. She had had repeated efforts of kidney stones and I said, you know, you really wanna think about how much spinach you're eating. You know, I'm not a physician, but if I was you, I would think about the quantities of spinach. She probably couldn't detoxify oxalates properly. Probably not, but I wanted you to comment about something that seems to be more and more epidemic with people. Problems with salicylates having to do with the peeling of vegetables, maybe eating fruits and vegetables that aren't ripe. Some of the other things we're seeing in the stores, and I just wondered if you'd research salicylates. I have not looked into that, but I need to now that you've mentioned it, but it's interesting. Thank you. Thank you. Thank you.