Part III Jeffrey Bland Bastyr Lecture June 2009

So why does this take so long to change beliefs? Well, if we actually go back to 1536, and that's why I'm so pleased that Brooklyn is here, because I love honoring our Canadian relatives. It was 1536 that Jacques Cartier from France, as you know, got his ship stuck in the St. Flores Seaway outside of Montreal in frozen winter. And they were all dying of scurvy, right? You know the story. And finally, they had been very respectful of the Indians there, the native first generation people, the British nation people, but finally the chief of the tribe, because he could see these men dying on the shipboard. And they knew these. The natives knew about what to do. And he came and he said, you need to make a tea of the bark of this tree, right? Which they did. It's called the arbor vitae tree. Today, it's the first tree brought from the Americas back to Europe. Arborvitae, the tree of life. And in that bark is, per 100 grams of bark, is about 45 milligrams of vitamin C. So if you make a tea of the bark, it only takes 5 milligrams to prevent scurvy. So you're going to have more than enough to cure scurvy. Now, you would say, how long does it take after you drink this tea, if your gums are bleeding and your joints are loose and you've got hemorrhages all over your skin? You know, it's a horrible way for these people to die. Tens of thousands of men were dying by this condition. How long does it take after drinking this tea? Sometimes less than a day. Less than a day. Their gums start healing, their hemorrhages start going away, their joints don't ache. I mean, we're talking about, like, cortisol or like antibiotics. I mean, it's just unbelievable. So then, you know, from 1536, it's all the way up to 1747 to Lynn, and then it's from 1747 up to Cook, and then from Cook to Vancouver. I mean, we have a lot of years here, right? Like, how much light do you need to eliminate the path? That's the question. So then we talk about metabolism. So how long does it take us to understand something about metabolism? Well, I'd like to go back to 1506 with Ulrich Pinder, who is a Dutch physician of some note in the 16th century. And Ulrich Pinder had made observations. I'm not saying he's the only one that done this. Certainly others had that urine color, smell and taste had something to do with the metabolism or health of that person. So he developed what was called the urine color wheel. It's the first metabolomic assessment tool that I could ever find in the reported literature. So each of these little vials is, you can't probably see it too well, but it's a color of a urine. And then down here it describes in Dutch exactly what the smell, taste and physiology, or they have names, diagnoses basically for these different conditions. Now you remember certainly their examples were with laughter and we're familiar about King George, remember? And what was that disease called? So if you have. It's a defect of red hemoglobin formation, wasn't it porphyria, Right, Porphyria. Right, porphyria. And one of this, one of the signs of porphyria is melanin's. And in the urine you can see it, right? And you can smell it. Now, the diagnosis of diabetes was made up until the 20th century on the basis of taste. Wouldn't you love to be a clinical chemist back then? So, you know, it's sweet urine, right? Sweet urine was the diagnosis for diabetes. So this, this concept that people differ in the way that they function based upon things that can be seen. It was a conceptually interesting concept then, mapping that against things like what effects are in the environment, like what they eat and how they live. How did that influence their metabolism? This is a pretty. We take this for granted today. We think, well, yeah, it's obvious. Well, it wasn't obvious for hundreds of years that these were connected. So now we go to the orthomolecular revolution. Here are my founding, in this case, fathers, although I am also going to talk about a mother here in a second. But there are four people that I want to highlight that I think are very important. One who is a Canadian and one of who is British and two of whom are from the States. So let's start with Sir Archibald Garrod, the father of genetic metabolism, diseases of infancy. Every student who's ever studied physiology has studied Garrod's work in one way or another. Maybe they didn't know that, but when I went back and reread his papers, his first paper published in the Lancet in 1902. If you read that today, you would say this is as Modern in 2009 as it was written in 1902. This man was totally brilliant. I mean, he was light years ahead of everybody. I don't even know how people probably even focused on what he was saying because literally he was talking about molecular groupings from which we sprang so 55 years before DNA was discovered. So I'm going to talk about Archibukarat for a second, then I'm going to talk about Roger Williams and I'll talk about Ice Pauling and Wesley. I'll talk about Ebert Hoffer. So Archibald Garad, the individuality of man. He is the person that's credited, at least in the English speaking literature as being the person who first discovered and used the term individuality as it related to metabolism. And so he discovered alkaptenuria, which is, as you know, one of the genetic metabolism diseases of infancy like Hartnett's disease, megaloblastic anemia, female ketonuria, Wilson's disease, Goucher's disease. You're familiar with these, right? These are genetically linked disorders. And so he, from making these discoveries recognized that there was very vast difference in the metabolism from person to person. Even though they all had 10 fingers and 10 toes and two eyes and they looked similar, that at the metabolic level there was very significant difference that you couldn't necessarily see just by looking at their presentation. So here is a reprint of his 1902 paper that appeared in the Lancet, the Incidence of Al Captainuri A case Individual, mechanical individuality. What he says, it's recently been pointed out by Bateson. Now, some of you probably don't know the history of genetics. Remember Gregory Mendel, we all studied him in school. The monk, Gregorian monk, that was doing the stuff with the peas. But can you imagine what the church thought about this concept of genetics when he started showing that there was this dominant recessive characteristic that was passed through it? It was all kind of like a math equation. You could make these charts out. I mean, this was like, hold on just a minute, God is making these decisions. This is not like some kind of arithmetic problem. What's going on here? Because there was a very strong resistance, wasn't there, to science infiltrating those. If you see the angels and demons, this is the whole theme of angels and demons, isn't it? This kind of interface between science and theology. So Mendel's work was basically blocked and key put away and was just a very small group of number of people knew about it. Then 100 years later, Gregory Bateson, a biologist of Great Torpedo, ultimately Nobel Prize winner, rediscovered Nindel and really made that accessible. So it was 100 years of kind of quiet about recessives and dominance. And then it reappeared with Bateson and became popular in the 20th century. So he says, if it be correct inference from the available facts that individuals of a species do not conform to an absolutely rigid standard of metabolism, meaning all of us are not the same, but differ slightly in their chemistry as they do in their structure. It is no more surprising that they should occasionally exhibit conspicuous deviations from the specific type of metabolism that is considered normal. Now that's a profound sentence. I don't know if that hits you like it hits me. I know I'm a chemist, so I tend to be inclined towards that kind of language. But what he's basically saying is we differ remarkably in the our chemistries, even though they might be considered normal people. Right, normal. But what does normal mean? Is it normal the same or normal within a Gaussian curve of distributions. So then the summary of this work, this was journal Inherent Disabilities published a few years ago, says his second book, Inborn Factors in Disease, was about inherited predisposition to disease. Chemical and metabolic individuality, which are the modalities of predisposition originating from the molecular groupings. In Garrod's view of life, such groupings as the interlocutor, molecular hybrids of low linked complementation and expression of modifier genes can assume varying expression in the heterozygotes. Now, what's that mean? What that means to me, if to make this language simple, is that, yes, our genes are there as templates for what we might be, but they don't tell us what we are. What tells us what we are is how our genes interact with our environment. From the moment the sperm meets the egg, the environment is the modifier for the expression of our genetic pluripotentiality into who we will become emotionally, physically, physiologically. So our genes are a potential but not an outcome. You follow what I'm saying? And the variation can be that of our environment that causes them to modify their expression.