Okay, so early on in the first few lectures, they see all sort of emphasize that our point of view is practical, okay. And for us, maybe we have this ambition, maybe of classifying final manifolds from this viewpoint, okay. And so what we wanna be able to do is we wanna be able to start with the simple side of the picture. So we wanna start with a phano polytope because that certainly seems a lot easier than to go away and try and find phano manifolds. And we've seen in this class that, you know, if you give me a phano polytope, then there are various things I can do to it, like I can mutate it. And that's just the QG deformation from, well, from one type of variety XP to another type of variety, XQ, okay. So that's one of the things we can do. And you know, this seems very successful. It preserves the period sequence and things like that. So yeah, I mean, this seems like a good thing to be doing. And it's all very good. But how on earth do we move from having a polytope to having a phano albifold, okay. So I guess the crucial question is, how do we get P or maybe XP to a phano albifold X? Just as crucial, how do we find the marrow F? And in general, we don't know. But fortunately, there's a large collection of cases where we can certainly do this. And what we do is we do the Hori-Vaffa construction backwards, okay. So one way we can do this, or so sometimes we can do this. I eat, we can find an X and an F via Laurent inversion. And so yesterday I gave you a whole series of examples that we're trying to illustrate this method. So yesterday's examples, I was starting with a polytope P and I was trying to find some way of assigning combinatorial data to P that allows me to sort of back build the Hori-Vaffa construction to recover the phano albifold X and the marrow F, okay. And when it works, it works really well. But making a sort of precise statement about when it works is not something that we really know how to do. So from the practical point of view, this is the best tool that we've got. Frankly, if it doesn't work, then you're in a world of pain, you have to really sort of struggle to do this. And fortunately, the vast majority of phano manifolds can be constructed in this way. So of the 105 phano refolds of Mario Mackay, I think it's at least 78 of them. Oh no, I don't have it written down. So I think at least 78 of them can be built as a tarot complete intersection. We're using techniques like this, okay. And there's the case of albifold delpetzels with a third one one singularities. In that case, we have 26 of these mutation equivalence class of polytopes and most of them on inversion are scaffolding. Like I said, when it doesn't, you've got a whole different problem, but it does seem to be the vast majority of cases. So it's not a sort of technique to be ignored. All right, so let me try and make precise what I think a scaffolding is. Definition. So characterise when, I don't know. Do you have a, but that's really just an obstruction to be in a TG. Yeah, we don't know, basically. Okay, so there is one issue, I'll explain it, why not. So in this case, it turns out there are actually 29 delpetzels with a third one one singularities, which is not equal to 26, okay. And so what's going on here? Well, these three additional cases have H naught empty. Okay, so this means they can't be of class TG. They can't admit a taric degeneration. And the ratio's point is so far, this is really the only obstruction that we know of. No, it's not actually, it's just nobody knows a model for which it works. That's all, yeah. Yeah, I know, I think Dom was asking whether they have H naught zero, which is not the case. Yeah, we just don't know if they have a complete intersection, description, definition. They find this process of Laurent inversion, a way of at least conjecturally moving from the polytope to X and the mirror F, okay. So I'm just, everything's happening in a lattice N and I'm gonna fix a basis for N for all time. So let's just fix a basis, B. Fix a partition of this basis for all time. So it's a partition S1, SC, and U of B. And I want these SIs non-empty. So I'm just gonna define SI to just be one of the SI circles and then I'm just gonna throw in the origin. I'm gonna define the simplex delta I to just be the convex hole of these points. So these delta I, they're basically just a collection of standard simplices. But then a strut, B, is just given by, so I'm gonna take each of these simplices in turn to allow myself to translate the simplex by one of its vertices, okay. I remember that the origin is one of the vertices and then I'm allowed to dilate it by some non-negative amount. And I'm gonna then take the Minkowski sum of this for every vertex and then the Minkowski sum of that for every strut, for every simplex. So as I try and move one of these simplices forever away from the origin, it necessarily becomes bigger and bigger and bigger. And then also, once I've done that, I'm gonna allow myself to translate the whole thing by this collection U of basis elements that we didn't use to construct simplices. So the U, thinking back to yesterday, are the unaliminated variables. And so here we need all the coefficients to be non-negative. So now let's award ourselves a final polytope inside that lattice. So let P be final polytope. Then a scaffolding on P with respect to this basis and this choice of partition is a collection of struts whose convex hull and the convex hull of the illuminated variables gives us P. No, I'm not, because this is just a point. So it's, yeah, these B's, they're also just points. So it's, yeah, sure, but so this is just a point. So all I'm doing is translating. So it's defined. Yeah, yeah, let me say that again in case some people didn't catch it. So this delta is indeed a simplex, okay? Then so we're just subtracting a point of it. So that's just the translation of this impact. That's no problem. Then we're dilating it. Then we're taking a bunch of Minkowski sums. And then finally, this is just a sum of a collection of points, so we can just translate again. That's defined by that. And then finally a scaffolding is just a collection of struts and the unaliminated variables that fill out P. So very much like we were doing in the examples yesterday. Let me just, using this notation, just do an example. So I'm gonna start with P that looks like this. I'm gonna describe a scaffolding on it. So the origin is sitting here and this whole thing is in N, R. And for those of you who've been keeping track, this is one of those third one, one polytopes. So the first thing is I need to fix a basis. So in this case, I'm gonna fix B to just B, zero one and one one. And now I need to choose my partition. Well, I'm just gonna have S naught to be zero one and I'm gonna have my unaliminated variables to be one one. So delta is just the convex hole of the origin and S naught. So delta is just a little line segment, a vertical line, unit line. And now I'm gonna pick some struts. So I'm gonna define two struts in this language but from the examples yesterday, I think you might know what I'm gonna do. So my first strut in this language is I'm gonna take three lots of delta and then I'm gonna subtract off one one. And then my second strut, I'm gonna take one lot of delta and I'm gonna subtract off zero one. So I've done two different things here. This first one, I've, if we look over that expression, I've taken delta and subtracted off the origin and then dilated by factor of three and then I've subtracted off my unaliminated variable. That can work out to be. The second one is slightly different. I've taken delta and subtracted off one of its vertices, dilated by factor of one and then subtracted off no copies of the unaliminated variables. So let me try and make that clearer. So in this case, my coefficients, my D's and my C's, I have D zero zero equal to three and D zero one is equal to zero. And C one one is equal to one. And in this case, I have D of zero zero is zero. I have D of zero one is one and C of one one. Yeah, there's no I because it's one. Yeah, sorry, just a bit lazy. And so this defines a scaffolding because P is equal to the convex hole of U union T one and T two. And if I just draw a picture of what the net result looks like, just like the pictures we were drawing yesterday, T one is along here, P two is here. And then my unaliminated variable and this circle here is my U delta would be this fine segment. Now the conditions that I've put on how to define the struct and how to define the scaffolding are basically just a bit of a con. It's so that the conditions we have in the Horry of Africa construction will be satisfied. Okay. And so one thing I can do is I can try and reinterpret what the divisor map D looks like in terms of this data. So let me just, just so we don't get into too much of a notational nightmare, let me define a couple of vectors. So for a struct T, we're going to record the coefficients D, A, I, C, B. Remember these are non-negative in some vectors. So in vectors. So D, I will just be the coefficients from the D, I, simplex, D is just going to be the coefficients from the other nominated variables. And I'm also going to define the sum of the DIs. So I'm going to write Li to just be the sum of the DIAs. And again, this is going to be a non-negative integer. Once I've done that associated to a scaffolding, we have a matrix. And it's a N by D plus C plus N. And this is just D. It just starts off by having an identity block. So in the Hori-Raffer construction, this identity block corresponds to the basis of L du. Then I'm going to just stick my vectors D in. So they just live here.  And how many of these do we have? We have, what did we say? It's a C of them. And then finally, I'm going to stick in my coefficients coming from the unordinated variable, the trade. Oh no, no, no, these are meant to be the vectors. I've indexed each vector by the index of the strut. So this is meant to be, yeah, this is meant to be the vector corresponding to the first strut. And then this is the vector corresponding to the empty strut. Yeah, I'll just write that down. So we're rows, yeah, indexed.  So I can write L, which is just going to be E's, L, L-i's, oh yeah, that's a really good point. Yeah, it's meant to be the dimension of N the lattice, it's the rank of the lattice. It should be the rank of the lattice. Okay, so there's the N block, then we have, okay, no, it's indeed the size of the lattice, shall I explain? So of course the N is from here, okay. It's because these have all got an extra point added into them, yeah, on the thing, I think at this point helped more than drawing what it is in this case. So let's try and do that. So the example continued. So in this case we're gonna have D is equal to, so there's two struts, so N is two, so it's gonna be a little identity block, and then I need to write down the first vector, which is free zero, and then for the second strut it's zero one, and then I write down the vector coming from the U, so that's one for the first strut and zero for the second strut, and I have in this case just one L, and for the first strut it's this sum, so it's free, and for the second strut it's this sum, so it's one. So from this collection we can also construct a Laurent polynomial. So to a strut T, associate a Laurent polynomial, and it's just gonna be given taking, oh it's gone now, hasn't it? Taking the definition of a strut, and turning all the additions into multiplications and our subtractions into the divisions and so on. So what we're gonna have is the product over all of the struts, sorry, the product over all of the sympathies, and then the product over the vertices of those sympathies, that's the first double sum, and then at multiplication becomes exponentiation, and subtracting off that point just becomes dividing by a monomial, and then the simplex delta i, we're just gonna reinterpret it as a sum of monomials, and then we need to subtract off the points of U, so that's the same thing as multiplying by the product of one over x to the Cb. That's really just a literal translation of the polytopal description into a strut of Laurent polynomial. And so by construction we have that it's Newton polytope is just equal to T.  So finally to a scaffolding T1 to Tn, we have, which is just gonna be the sum of these FT's. And then if you remember, I have to add on the unaliminated variables, so I just do, and by construction, because this is a scaffolding for P, we have that the Newton polytope of F is equal to P. And the way I've set this up, if the hori of affer construction is gonna work for this divisor data in this collection of line bundles, then this should be the mirror that the hori of affer method works. Okay, so I'm gonna have to stop on that ratio takeover, leaving a bit in the verge. Okay, so can you hear me? Let me sort of try to wrap this up somehow. I can clear this board. And let me remind myself, what are we doing? So we started out with a polygon polytope P, yeah, polytope polytope. And then we, I'll told you what's a scaffolding of P and then associated, okay, so maybe I'm gonna summarize this as one, sorry, associated to a scaffolding, we have one N times D plus C plus N matrix D plus some column vectors, L, I's. And what that gives us is the A, D, and these L, I's, this is the data, complete intersection, X and F, some dark variety, giving a scaffolding, we have a complete intersection data. And then Al has also told you how to make a lo-ranpoin. Again, that would be, if you like, the same sentence here, associated to a scaffolding in T1TN, we have one complete intersection data, and two lo-ranpoin, and two are mirror to each other. They are so under the Horewaf construction. Let me sort of point out, if you start with a polytope and the scaffolding on it, there will be some assumptions, some further assumption on that scaffolding that would ensure, for instance, that X is a quasi smooth and well-formed orbital, and well-formed orbital, and we don't really know what those assumptions are. We do this on examples, in most cases, when we do it, X is well-formed quasi smooth orbital, but sometimes it isn't. There's another thing about this construction. Okay, so in some sense, this is a kind of conclusion, okay, except that we'll further wrap it up later, in a moment, but then let me say another feature of this construction. There is further this construction. Let me say it in words, and then I will make it a bit more precise. Actually, from the polytope P, you can form the final variety, the historic final variety, XP, and XP is one of these complete intersections in F, is a member of those complete intersections, of the family of complete intersections, and we can write down its equation, and let me tell you how to write it down. Suppose that I do the scaffolding, and then I get this data here, then XP is one of these. It's one of these, yes. No, no, it's one of these. There, family, the one given by the scaffolding. And so, we'll introduce variables corresponding to the columns of the matrix D, as we always do. And so, this is an N by, I would like to say, not D plus C plus N, but N plus D plus C matrix, okay? So, I'm gonna call the first N columns Y1 up to YN, okay? Then these guys, there are D of these, and so, I'm gonna call these ones YN plus one, all the way to YN plus D, and then these guys N plus D plus one, all the way to YN plus D plus C, okay? So, we introduce variables Y1 up to YN plus D plus C, corresponding to the columns of D. Yeah, it is the size of the vector C. It is the size of the vector C. And how many S's do you have? Yes. Exactly. For each one of those, I have one column at the end, because, sorry, that's correct. In fact, okay, okay, right, right. You are right. So, what do you wanna call it K? What's D for you? What's D for you?  Okay, so in fact, actually there are a few more variables then, because the uneliminated variables are even beyond that, it seems to me. The size of U, and I have to append it at the end of everything, and I'll just do all this stuff, in other words. No, wait a minute, no, no, I don't know, because I have to do something now that has to make sense, and you know, if, why didn't you ask Al about this? No, no, there is, I think there is a K here, or a U maybe, okay, right. There is an identity, there is an identity. You're paying just at the wrong time. Sorry, I mean, so at the beginning, there is these S I knots, okay. Okay, so there are C of them. They form a partition of, together with you, I see. I see, I see, I see, I see, I see.  The dimension of N was D, okay. And this is somehow the thing that I don't terribly like. So I want this to be K plus E, and then, indeed, absolutely. And then I want to be something like this, so I want to say that K plus C equal H, so to speak, okay. And then I want to call these guys all the way to Y, N plus H. And then here, H plus one, all the way to H plus U, okay. Maybe now you agree with me. Anyway, so this is all some large academic, because I'm just going to write down two monomials now, binomials, C, C, I'm going to write, ha ha, C binomials. And so I'm going to write like this, hopefully, let's see. Or I, in Y and C, I'm going to write binomials like this, product J in S, I, Y, N plus J. And then minus product K equal one to N, one to N of YK to the, and my claim, the claim here is that these binomials define XP in F as a complete intersection of the correct limons. Let me try to wrap it up, wrap it all up. So remember at the beginning, we spoke, I told you in fact, about this mirror symmetry program. And so, you know, mirror symmetry, as I said, is about torque degeneration. We always start a final part of P, and then we want to understand enumerate, classify whatever, study, understand, we call this families M, of deformations. Of XP to a final orbital. And then to each of these families, or each of these families, attach the random polynomial F in, you know, C, Cp is a polytope in NR, and we want F in C bracket N with mute F equal P, okay? Okay? And there is a certain mutation in variance to these things. And so we want to be able to say things like that, for instance, for two different polytopes, P and Q, then the final XP and the final XQ deforming the same family, M, we want to be able to say that that's if and only if the corresponding mirrors F and G differ by a chain of mutations, those algebraic mutations of Laurent polynomials to the family of deformations of XP to an only. Okay, so they are attached to the polytop and the family. They're attached to the polytop and the family. And, you know, this implies it's stronger than saying that P and Q differ by chain of mutations, okay? So this is what we're working on, and we're working on some of the theory of this, okay? But we're especially interested in the practice of this. What did I say at the beginning, these lectures that we would do? Well, I promised that it would give you some practical things that works sometimes. And that's what we've done. So here's what we actually did. So start from P, okay? We defined this notion of scaffolding.  But in fact, these things are reasonable, okay? You can draw pictures of them and, you know, that makes sense. And out of the scaffolding, a scaffolding gives one a family of total complete intersections. And XP is a member of that family. And so in good cases, the general member of that family is a well-formed orbifold. So this sort of answers part of question one. You know, I don't understand the whole family, but here's a way to give, to write at least one family down. And indeed, it gives this mirror Laurent Poirot. So we can see that at least this goes some way in doing what we want to do. That's it, really. We didn't really talk much about three. We don't understand too well where we're working on it, but it's not so, so we can, we can, this is more like a question, okay? So in practice, but it doesn't work very well, okay? I'll just put it like this. But, so given a polytope P, you can look at various mutations of P. And typically in that mutation class, very few polytopes will admit scaffoldings. That sort of answers your question. No, no, let me just work out whether I'm finished with everything, or whether I want to say something more. Well, I suppose that, you know, maybe I was somewhat defense. I mean, in practice, even though this is limited, not all deformations are into a complete discussion. This is a fact. And we know several examples of that in some sense that's the most interesting case. Nonetheless, if you are interested in doing the yellow pages of all possible final LG pairs, this works.  It's not a theorem. It's a feeling. We, you know, in the, in the corners that we've been looking at, we were able to fill almost all the table using this method. And then there is a few extra cases where you have to work much harder. And perhaps at this point, I can't stop. I've stopped. That's it.


So, for those of you who have not heard of the Corel Personalized Medicine Collaborative, this is a longitudinal research study that started in 2007. And really the aim of the study is to understand the utility of receiving personal genome information. We are genotyping individuals, providing it back to, results back to participants, and doing a series of follow-up behavioral studies to determine what they're doing with that information. So are they changing their diet or lifestyle based on that information? Are they sharing the information with their health care provider, and is their health care provider making any recommendations, ordering any tests, changing their care or management in any way? In addition, we're looking to identify new genetic sites that are associated with common medical conditions and drug response. As I said, the study was launched in 2007, and at this point we have more than 6,000 participants that have enrolled. Just briefly how the study works, participants, the majority of our participants have been enrolled through group informed consent sessions. Individuals actually come to the Corel Institute or other group sessions that we've held. At the end of an informed consent presentation, they, if they choose, sign the consent form and spit into a tube, which is always nice in a group setting. Everybody loves that. After they have provided their sample, they then receive an online activation, and the remainder of the study is really conducted via the Internet. People create a personalized account, they fill out a series of required questionnaires, including family history, medical history, lifestyle, demographics. And once they have completed those required questionnaires, they're put in the queue for genotyping. We do our genotyping using the Affymetric 6.0 and DMAT chips currently. And then once results are generated based on those genotyping platforms, we are ready to release results. But here's the caveat. An important component of the consent process is that participants consent to only receiving results that are approved by our advisory group called the Inform Cohort Oversight Board. And I'll go into greater detail. So this is sort of a vetting process for how we will determine what results to report to participants. So that's going to be the crux of the talk, and let me just finish sort of the general outline of the study, and then I'll go into greater detail about that. So once that group approves, what results will be reported, reports are prepared, and they are pushed out to participants through this secure web portal. Participants get an email that says a new result is ready, but none of their results are communicated via email. They're always pushed to go to log on to the secure web portal to view their personal genomic information. After they view that information, they can contact us to speak with a genetic counselor. We also have a pharmacist coach network so that if they have questions about their pharmacogenomic results, they can speak with a pharmacist as well. And we follow up with a series of online questionnaires, again, asking them what they did with the information. Was it useful? Did it prompt any anxiety? Did they actually share the information with their health care provider because the information is going directly to a participant? So I just want to talk a little bit about, because the focus of this session is selecting variants for the return, I want to talk a little bit about how we go through that process. We, the Corial staff actually selects what variants we want to put forward to our advisory group. And there are a series of technical guidelines which I'll discuss that guide that selection process. We then prepare a report that goes to two different advisory groups, our ICOB and Form Cohort Oversight Board and our Pharmacogenomics Advisory Group. Only those drug gene pairs that would relate to drug metabolism will go to the Pharmacogenomics Advisory Group. Everything does go to the ICOB. The ICOB reviews and approves or disapproves, rejects what we've put forward to them. Obviously only those things that are approved go, moves forward to report development and then the deployment of the report to participants. So we have two sets of technical guidelines, one for health conditions and one for drug gene pairs. And it's a fairly in depth process. This was published by one of our colleagues, Cappy Stack, earlier this year. So we go through a literature search for all of the, looking at published GWAS. We will only select studies that, variants that have been replicated across multiple studies, moderately sized studies. And we do have minimum cutoffs for the number of participants that need to be included. And we're looking for variants that have been associated with common complex diseases, not traits. So we had actually originally considered putting forward things, variants that have been associated with things like height or eye color. And have since rejected that idea, those types of variants are not included in the study. Once we've identified disease associated variants, we go through a process of selecting a single variant per health condition currently. And looking at variant selection hierarchy, we rate each variant that we've identified as potentially worthy of inclusion, based on whether or not it's been looked at through a meta-analysis in multiple studies, replication in multiple independent studies, or replication in multiple cohorts in a single study. We take all of that data, compile it into a nice report, and summarize it for the informed cohort oversight board. And only, obviously, only those conditions with valid genetic associations are passed through that process. From the standpoint of pharmacogenomics, this is a slightly different process. We're looking to identify and select drugs and key genes that are associated. We do this by reviewing published literature as well as public databases, including the FDA table of drugs and biomarkers, PubMed, PharmGKB, the CIP 450 drug interaction table, national prescription data, and also our own population and the reported medication use. Obviously, we're not as interested in reporting on a drug gene pair where there's one person in our entire cohort that's on that particular medication. This wouldn't be of interest to the population. And as a result, setting utility wouldn't be very interesting. We also review published and public data drug metabolism pathways, PubMed, again, PharmGKB, and the CIP allele nomenclature database. Based on all that, we try to define key alleles and haplotypes and identify a minimum set of defining variants for those haplotypes, and then select haplotypes for inclusion based on evidence scoring. So the evidence scoring is a detailed process. We rate different studies based on the greatest to, obviously, the lowest evidence, based on whether or not there have been clinical outcome studies conducted, the available pharmacokinetic and pharmacodynamic studies, molecular and cellular functional studies, and genetic variant screening studies. So this goes into a complex scoring process that goes from 1 to 13. Variants that have been only seen in one study, such as a case report, will not be included. If there is functional data that suggests that the particular variant or haplotype or gene directly impacts the metabolism of the drug of interest that is rated more highly than if the gene is associated with a drug that is related, but not the one that we're particularly interested in. Obviously, this is a complex process that I won't go into in detail, but I'm happy to talk with anyone afterwards about the strength of evidence scoring system. So those are the technical guidelines that guide the selection of variants and drugs and health conditions that we put forward to the ICB and the PAG. But just want to briefly talk about that process itself. So we have the informed cohort oversight board. This is an external advisory board. There are no voting members from COREAL. It's composed of scientists, medical professionals, ethicists, and community members. This is modeled after CAHANA's ICOB concept that was published in Science in 2007, where an expert group would review drug gene pairs, and that would be used to determine what information could be reported back to participants. So COREAL's informed cohort oversight board consists of many notable scientists, some of whom are in the room. And actually, this group just met this past Monday. Their charge specifically is to determine whether each health condition or gene involved in drug metabolism is at minimum potentially actionable, and I know David just said he hates that term. It's hard to say what the cutoff should be.  But because we want to look at the potential utility of this information, we felt like some level of actionability was needed, so we have provided the ICOB with some guidance with respect to that. In addition, they're also charged with determining whether or not the genetic associations that we're proposing are statistically valid. The Pharmacogenomics Advisory Group is a separate board, and they are specifically chosen based on their expertise in pharmacogenomics. They provide recommendations to the ICOB, so their decision alone does not determine what goes out to participants, and this group is composed of pharmacists, pharmacologists, ethicists, and clinicians. Again, we have members of this group in the room and certainly appreciate their service. Their charge is similar, but a little bit different, so it's to determine whether or not there's sufficient evidence to support the role of each gene in the metabolism of the proposed drug, whether the impact of one or more haplotypes is clinically relevant with respect to the proposed drug, and whether the drug pair is potentially actionable. Again, the workflow of the ICOB and the Pag is that although both review these submissions, the decisions of the Pag are then submitted to the ICOB for approval, and there are cases where the ICOB does overturn a recommendation or rejects a recommendation of the Pag. Just a list of the currently approved diseases and drug metabolism pairs that have been approved by the ICOB so far, and acknowledgments of the staff and ICOB and Pag that participate in this project. Thank you. Time for a couple of questions or comments now, and then the session is interrupted by lunch, but we have three speakers after lunch and then a longer discussion session at the end of the session. Howard? Just a quick point of clarification. You had indicated that a single variant would be chosen per condition. Do you mean that at a site where there are lots of different variants that are in the same haplotype block, you're only selecting one SNP? Or do you mean for a common complex disease, you will choose one and only one variant? So for example, in the case of diabetes, this gives me some concern given the plethora of potentially relevant variants that exist. So thank you. It's an important clarification. So for common complex diseases, we are currently only reporting on a single variant, and it certainly is concerning given the multigenic models that are coming out and the number of different variants that are known to contribute to the risk of these common complex diseases. At this point, we are working on coming up with a multigenic algorithm that would be approval by the ICOB, not at this past ICOB meeting, but at the previous one, we had put forward some multigenic models, and the problem that we ran into is that they're not replicated. And so although we all agree that there are multiple validated and replicated variants associated with each of these common diseases, how do you put forward, are we going to give people 50 different variants and make them process that? We'd prefer to give people a multigenic risk, but none of those models have been validated. Do you choose a model that has multiple validated variants within it? And so we're still trying to think through that process. In the meantime, we certainly see it as a limitation. We make it clear on our reports that it's a limitation. We're only providing you a very small insight into the many genetic risk factors that contribute to this, but at this point, we feel like it's one approach. I will say that for pharmacogenomics, we are using multiple variants and reporting on using the star nomenclature that's commonly accepted. Can you comment on, so this is great work, and it does seem like it takes a lot of effort. Can you comment on the amount of effort it takes and how this can scale? So for example, at different institutions that are tackling these same issues, typically you can get together a committee, but then it ends up, well, maybe we discuss one whatever is hot in that particular month. How can the scale, and for example, do you make your knowledge available to others to be able to use at other institutions? And if not, how do you sort of see this scaling beyond this particular initiative? So that's a great question, and is one that is discussed routinely by our advisory groups. The amount of preparation work that goes into each of the ICOB impact meetings is absolutely enormous on the part of the staff at Corel, because we really feel like as an advisory group, they shouldn't need to go out and do all of the legwork to try and determine this, but we should present it to them and they should be evaluating it with additional supplemental material if needed. Currently, we give them on average, I would say, four either health conditions or drug gene pairs to evaluate at each meeting. We would need an army of staff in order to scale this up, and so one possibility would be, as ideas like this pick up momentum at different institutions as having different groups of people working and sharing their knowledge across different institutions, I think we are happy to share our model. We have always said that we would make the decisions of the PAG transparent and we can certainly discuss sharing the submission materials with other institutions so that there is some collaboration and everyone isn't reinventing the wheel. I think we are going to have to move on to our next speaker. Thank you.


Section 1 of Ingersoll on Thomas Paine from the works of Robert G. Ingersoll, Volume 1, Lecture 3. This is a LibriVox recording. All LibriVox recordings are in the public domain. For more information or to volunteer, please visit LibriVox.org. Recording by William Jones, Benita Springs, Florida. Lecture 3, Thomas Paine. Section 1. Thomas Paine. With his name left out, the history of liberty cannot be written. To speak the praises of the brave and thoughtful dead is to me a labor of gratitude and love. Through all the centuries gone, the mind of man has been beleaguered by the mailed hosts of superstition. Slowly and painfully has advanced the army of deliverance. Hated by those they wish to rescue, despised by those they were dying to save, those grand soldiers these immortal deliverers have fought without thanks, labored without applause, suffered without pity, and they have died, executed, and abhorred. For the good of mankind they accepted isolation, poverty, and calumny. They gave up all, sacrificed all, lost all but truth and self-respect. One of the bravest soldiers in this army was Thomas Paine, and for one I feel indebted to him for the liberty we are enjoying this day. Born among the poor were children of burdens, in a country where real liberty was unknown, where the privileges of class were guarded with infinite jealousy, and the rights of the individual trampled beneath the feet of priests and nobles. Where to advocate justice was treason, where intellectual freedom was infidelity, it is wonderful that the idea of true liberty ever entered his brain. Poverty was his mother, necessity his master. He had more brains than books, more sense than education, more courage than politeness, more strength than polish. He had no veneration for old mistakes, no admiration for ancient lies. He loved the truth for truth's sake, and for man's sake. He saw oppression on every hand, injustice everywhere, hypocrisy at the altar, venality on the bench, tyranny on the throne. And with a splendid courage he espoused the cause of the weak against the strong, of the enslaved many against the titled few. In England he was nothing. He belonged to the lower classes. There was no avenue open for him. The people hugged their chains, and the whole power of the government was ready to crush any man who endeavored to strike a blow for the right. At the age of thirty-seven, Thomas Paine left England for America with a high hope of being instrumental in the establishment of a free government. In his own country he could accomplish nothing. Those two vultures, church and state, were ready to tear in pieces and devour the heart of anyone who might deny their divine right to enslave the world. Upon his arrival in this country he found himself possessed of a letter of introduction signed by another infidel, the illustrious Franklin. This and his native genius constituted his entire capital, and he needed no more. He found the colonies clamoring for justice, whining about their grievances upon their knees at the foot of the throne, employing that mixture of idiocy and insanity towards the third, by the grace of God for a restoration of their ancient privileges. They were not endeavouring to become free men, but were trying to soften the heart of their master. They were perfectly willing to make brick if a pharaoh would furnish the straw. The colonists wished for, hoped for, and prayed for reconciliation. They did not dream of independence. Paine gave to the world his common sense. It was the first argument for separation, the first assault upon the British form of government, the first blow for a republic, and it aroused our fathers like a trumpet's blast. He was the first to perceive the destiny of the new world. No other pamphlet ever accomplished such wonderful results. It was filled with argument, reason, persuasion, and unanswerable logic. It opened a new world. It filled the present with hope and the future with honour. Everywhere the people responded, and in a few months the Continental Congress declared the colonies free and independent states. A new nation was born. It is simple justice to say that Paine did more to cause the declaration of independence than any other man. Neither should it be forgotten that his attacks upon Great Britain were also attacks upon monarchy, and while he convinced the people that the colonies ought to separate from the mother country, he also proved to them that a free government is the best that can be instituted among men. In my judgment Thomas Paine was the best political writer that ever lived. What he wrote was pure nature. His soul and his pen went together. Ceremony, pageantry, and all the paraphernalia of power had no effect upon him. He examined into the why and wherefore of things. He was perfectly radical in his mode of thought. Nothing short of the bedrock satisfied him. His enthusiasm for what he believed to be right knew no bounds. During all the dark scenes of the revolution, never for one moment did he despair. Year after year his brave words were reigned through the land, and by the Bivouac fires that weary soldiers read the inspiring words of common sense, filled with ideas sharper than their swords, and consecrated themselves anew to the cause of freedom. Paine was not content with having aroused the spirit of independence, but he gave every energy of his soul to keep that spirit alive. He was with the army, he shared its defeats, its dangers, and its glory. When the situation became desperate, when glooms settled upon all, he gave them the crisis. It was a cloud by day and a pillar of fire by night, leading the way to freedom, honor, and glory. He shouted to them, These are the times that try men's souls. The summer soldier and the sunshine patriot will, in this crisis, shrink from the service of his country. But he that stands it now, deserves the love and thanks of man and woman. To those who wish to put the war off to some future day, with a lofty and touching spirit of self-sacrifice, he said, every generous parent should say, If there must be a war, let it be in my day, that my child may have peace. To the cry that Americans were rebels, he replied, Quote, he that rebels against reason is a real rebel. But he that in defensive reason rebels against tyranny has a better title to Defender of the Faith than George III. Some said it was not to the interest of the colonies to be free. Payne answered this by saying, To know whether it be the interest of the continent to be independent, we need ask only this simple easy question. Is it the interest of a man to be a boy all his life? He found many who would listen to nothing, and to them he said that to argue with a man who has renounced his reason is like giving medicine to the dead. This sentiment ought to adorn the walls of every orthodox church. There is a world of political wisdom in this. England lost her liberty in a long chain of right reasoning from wrong principles. And there is real discrimination in saying the Greeks and the Romans were strongly possessed of the spirit of liberty, but not the principles. For at the time that they were determined not to be slaves themselves, they employed their power to enslave the rest of mankind. In his letter to the British people, in which he tried to convince them that war was not to their interest, occurs the following passage, brim full of common sense. War never can be the interest of a trading nation. Any more than quarreling can be profitable to a man in business. But to make war with those who trade with us is like setting a bulldog upon a customer at the shop door. The writings of Paine fairly glitter with simple compact logical statements that carry conviction to the dullest and most prejudiced. He had the happiest possible way of putting the case and asking questions in such a way that they answer themselves in stating his premises so clearly that the deduction could not be avoided. Day and night he labored for America month after month, year after year he gave himself to the great cause until there was a government of the people and for the people, and until the banner of the stars floated over a continent redeemed and consecrated up to the happiness of mankind. At the close of the revolution no one stood higher in America than Thomas Paine. The best, the wisest, the most patriotic were his friends and admirers, and had he been thinking only of his own good he might have rested from his toils and spent the remainder of his life in comfort and in ease. He could have been what the world is pleased to call respectable. He could have died surrounded by clergymen, warriors and statesmen. At his death there would have been an imposing funeral miles of carriages, civic societies, salvos of artillery, a nation in mourning and above all a splendid monument covered with lies. He chose rather to benefit mankind. At that time the seeds sown by the great infidels were beginning to bear fruit in France. The people were beginning to think. The eighteenth century was crowning its gray hairs with the wreath of progress. On every hand science was bearing testimony against the church. Voltaire had filled Europe with light. Tolbach was given to the elite of Paris the principles contained in his system of nature. The encyclopedist had attacked superstition with information for the masses. The foundation of things began to be examined. A few had the courage to keep their shoes on and let the bush burn. Miracles began to get scarce everywhere the people began to inquire. America had set an example to the world. The word liberty was in the mouths of men and they began to wipe the dust from their knees. The dawn of a new day had appeared. Thomas Paine went to France into the new movement he threw all his energies. His fame had gone before him and he was welcomed as a friend of the human race and as a champion of free government. He had never relinquished his intention of pointing out to his countrymen the defects, absurdities and abuses of the English government. For this purpose he composed and published his greatest political work, The Rights of Man. This work should be read by every man and woman. It is concise, accurate, natural, convincing and unanswerable. It shows great thought and intimate knowledge of the various forms of government, deep insight into the very springs of human action and the courage that compels respect and admiration. The most difficult political problems are solved in a few sentences. The venerable arguments in favor of wrong are refuted with a question, answered with a word. For forcible illustrations, apt comparison, accuracy and clearness of statement, and absolute thoroughness, it has never been excelled. The fears of the administration were roused and Paine was prosecuted for libel and found guilty. And yet there is naughty sentiment in the entire work that will not challenge the admiration of every civilized man. It is a magazine of political wisdom and arsenal of ideas and an honor not only to Thomas Paine, but to human nature itself. It could have been written only by the man who had the generosity, the exalted patriotism and the goodness to say, The world is my country and to do good is my religion. There is, in all the utterances of the world, no grandeur, no sublimer sentiment. There is no creed that can be compared with it for a moment. It should be wrought in gold, adorned with jewels and impressed upon every human heart. The world is my country and to do good my religion. In 1792 Paine was elected by the department of Calais as their representative in the National Assembly. So great was his popularity in France that he was selected about the same time by the people of no less than four departments. Upon taking his place in the assembly he was appointed as one of a committee to draft a constitution for France. Had the French people taken the advice of Thomas Paine there would have been no reign of terror. The streets of Paris would not have been filled with blood. The revolution would have been the grandest success in the world. The truth is that Paine was too conservative to suit the leaders of the French Revolution. They, to a great extent, were carried away by hatred and a desire to destroy. They had suffered so long they had borne so much that it was impossible for them to be moderate in the hour of victory. Besides all this the French people had been so robbed by the government, so degraded by the church that they were not fit material with which to construct a republic. Many of the leaders longed to establish a beneficent and just government but the people asked for revenge. Paine was filled with a real love for mankind. His philanthropy was boundless. He wished to destroy monarchy, not the monarch. He voted for the destruction of tyranny and against the death of the king. He wished to establish a government on a new basis, one that would forget the past, one that would give privileges to none and protection to all. In the assembly, where nearly all were demanding the execution of the king, where to differ from the majority was to be suspected and where to be suspected was almost certain death. Thomas Paine had the courage, the goodness and the justice to vote against death. To vote against the execution of the king was a vote against his own life. This was the sublimity of devotion to principle. For this he was arrested, imprisoned, and doomed to death. Search the records of the world and you will find but few sublimer acts than that of Thomas Paine voting against the king's death. He, the hater of despotism, the abhorrer of monarchy, the champion of the rights of men, the Republican accepting death to save the life of a deposed tyrant of a Thurmus king.  All his life he had been the disinterested friend of man. He had labored not for money, not for fame, but for the general good. He had aspired to no office and asked no recognition of his services but had ever been content to labor as a common soldier in the army of progress. Confining his efforts to no country looking upon the world as his field of action filled with a genuine love for the right he found himself imprisoned by the very people he had striven to save. Had his enemies succeeded in bringing him to the block he would have escaped the column knees and the hatred of the Christian world. In this country at least he would have ranked with the proudest names. On the anniversary of the declaration his name would have been upon the lips of all orators and his memory in the hearts of all the people. Thomas Paine had not yet finished his career. He had spent his life thus far in destroying the power of kings and now he turned his attention to the priests. He knew that every abuse had been embalmed in scripture that every outrage was in partnership with some holy text. He knew that the throne sculpted behind the altar and both behind a pretended revelation from God. By this time he had found that it was a little used to free the body and leave the mind in chains. He had explored the foundations of despotism and had found them infinitely rotten. He had dug under the throne and it occurred to him that he would take a look behind the altar. The result of his investigations was given to the world in the age of reason. From the moment of his publication he became infamous. He was columnated beyond measure to slander him was to secure the thanks of the church. All his services were instantly forgotten, disparaged or denied. He was shunned as though he had been a pestilence. Most of his old friends forsook him. He was regarded as a moral plague and at the bare mention of his name the bloody hands of the church were raised in horror. He was denounced as the most despicable of men. Not content with following him to his grave they pursued him after death with redoubled fury and recounted with infinite gusto and the satisfaction they supposed horrors of his deathbed. Gloryed in the fact that he was forlorn and friendless and gloated like fiends over what they supposed to be the agonizing remorse of his lonely death. It is wonderful that all his services were thus forgotten. It is amazing that one kind word did not fall from some pulpit. That someone did not accord to him at least honesty. Strange that in the general denunciation someone did not remember his labor for liberty. His devotion to principle is zeal for the rights of his fellow men. He had by brave and splendid effort associated his name with the cause of progress. He had made it impossible to write the history of political freedom with his name left out. He was one of the creators of light, one of the heralds of the dawn. He hated tyranny in the name of kings and in the name of God with every drop of his noble blood. He believed in liberty and justice and in the sacred doctrine of human equality. Under these divine banners he fought the battle of his life. In both worlds he offered his blood for the good of man. In the wilderness of America, in the French assembly, in the somber cell waiting for death he was the same unflinching, unwavering friend of his race, the same undaunted champion of universal freedom. And for this he has been hated. For this the church has violated even his grave. This is enough to make one believe that nothing is more natural than for men to devour their benefactors. The people in all ages have crucified and glorified. Whoever lifts his voice against abuses, whoever arraigns the past at the bar of the present, whoever asks the king to show his commission or questions the authority of the priest, will be denounced as the enemy of man and God. In all ages reason has been regarded as the enemy of religion. Nothing has been considered so pleasing to the deity as a total denial of the authority of your own mind. Self-reliance has been thought a deadly sin. And the idea of living and dying without the aid and consolation of superstition has always horrified the church. By some unaccountable infatuation belief has been, and still is, considered of immense importance. All religions have been based upon the ideas that God will forever reward the true believer and eternally damn the man who doubts or denies. Belief is regarded as the one essential thing. To practice justice, to love mercy, is not enough. You must believe in some incomprehensible creed. You must say, once one is three and three times one is one. The man who practiced every virtue but failed to believe was executed. Nothing so outrageous of feelings of the church as a moral unbeliever. Nothing so horrible as a charitable atheist. End of Section 1 Section 2 of Ingersoll on Thomas Paine This LibriVox recording is in the public domain. Recording by William Jones, Benita Springs, Florida. Lecture 3 Thomas Paine, Section 2 When Paine was born the world was religious. The pulpit was the real throne and the churches were making every effort to crush out of the brain the idea that it had the right to think. The splendid saying of Lord Bacon that the inquiry of truth which is the love-making or wooing of it. The knowledge of truth which is the presence of it and the belief of truth which is enjoying of it are the sovereign good of human nature. Has been and ever will be rejected by religionists. Intellectual liberty is a matter of necessity for ever destroys the idea that belief is either praise or blame worthy and is wholly inconsistent with every creed of Christendom. Paine recognized this truth. He also saw that as long as the Bible was considered inspired this infamous doctrine of the virtue of belief would be believed and preached. He examined the scriptures for himself and found them filled with cruelty, and immorality. He again made up his mind to sacrifice himself for the good of his fellow man. He commenced with the assertion that any system of religion that has anything in it that shocks the mind of a child cannot be a true system.  No wonder the church began to hate him. He believed in one God and no more. After this life he hoped for happiness. He believed that true religion consisted in doing justice, loving mercy, in endeavoring to make our fellow creatures happy and in offering to God the fruit of the heart. He denied the inspiration of the scriptures. This was his crime. He contended that it is a contradiction in terms to call anything a revelation that comes to a second hand, either verbally or in writing. He asserted that revelation is necessarily limited to the first communication and that after that it is only an account of something which another person says was a revelation to him. We have only his word for it, as it was never made to us. This argument never has been and probably never will be answered. He denied the divine origin of Christ and showed conclusively that the pretended prophecies of the Old Testament had no reference to him whatever, and yet he believed that Christ was a virtuous and amiable man, that the morality he taught in practice was of the most benevolent and elevated character and that it had not been exceeded by any. Upon this point he entertained the same sentiments now held by the Unitarians and in fact by all the most enlightened Christians. In his time the church believed and taught that every word in the Bible was absolutely true. Since his day he has been proven false in its cosmogony, false in its astronomy, false in its chronology, false in its history, and so far as the Old Testament is concerned, false in almost everything. There are but a few, if any, scientific men who apprehend that the Bible is literally true, who on earth at this day would pretend to settle any scientific question by a text from the Bible. The old belief is confined to the ignorant and zealous. The church itself will before long be driven to occupy the position of Thomas's pain. The best minds of the Orthodox world today are endeavoring to prove the existence of a personal deity. All other questions occupy a minor place. You are no longer asked to swallow the Bible bowl. Well, Jonah and all, you are simply required to believe in God and pay your purant. There is not now an enlightened minister in the world who will seriously contend that Samson's strength was in his hair or that the necromancers of Egypt could turn water into blood and pieces of wood into serpents. These follies have passed away, and the only reason that the religious world can now have for disliking pain is that they have been forced to adopt so many of his opinions. Pain thought the barbarities of the Old Testament inconsistent with what he deemed to be the real character of God. He believed that murder, massacre, and indiscriminate slaughter had never been commanded by the deity. He regarded much of the Bible as childish, unimportant, and foolish. The scientific world entertains the same opinion. Pain attacked the Bible precisely in the same spirit in which he had attacked the pretensions of kings. He used the same weapons. All the pop in the world could not make him cower. His reason knew no holy of holies except the abode of truth. The sciences were then in their infancy. The attention of the really learned had not been directed to an impartial examination of our pretended revelation. He was accepted by most as a matter of course. The church was all powerful and no one unless thoroughly imbued with the spirit of self-sacrifice thought for a moment of disputing the fundamental doctrines of Christianity. The infamous doctrines that salvation depended upon belief upon a mere intellectual conviction was then believed and preached. The doubt was to secure the damnation of your soul. This absurd, devilish doctrine shocked the common sense of Thomas Paine and he denounced it with a fervor of honest indignation. This doctrine, although infinitely ridiculous, has been nearly universal and has been as hurtful as senseless. For the overthrow of this infamous tenet, Paine exerted all his strength. He left few arguments to be used by those who would come after him and to use none that have been refuted. The combined wisdom and genius of all mankind cannot possibly conceive of an argument against liberty of thought. Neither can they show why anyone should be punished either in this world or another for acting honestly in accordance with reason. And yet a doctrine with every possible argument against it has been, and still is, believed and defended by the entire Orthodox world. Can it be possible that we have been endowed with reason simply that our souls may be caught in its toils and snares that we may be led by its false and elusive glare out of the narrow path that leads to joy into the broad way of everlasting death? Is it possible that we have been given reason simply that we may, through faith, ignore its deductions and avoid its conclusions? Not the sailor to throw away his compass and depend entirely upon the fog? If reason is not to be depended upon in matters of religion, that is to say, in respect of our duties to the deity, why should it be relied upon in matters respecting the rights of our fellows? Why should we throw away the laws given to Moses by God himself and have the audacity to make some of our own? How dare we drown the thunders of Sinai by calling the eyes and nose in a petty legislature? If reason can determine what is merciful, what is just, the duties of man to man, what more do we want either in time or eternity, down, forever down, with any religion that requires upon its ignorant altar the sacrifice of the goddess reason, that compels her to abdicate forever the shining throne of the soul, drips from her form the imperial purple, and snatches from her hand the scepter of thought and makes her the bond woman of a senseless faith? If a man should tell you that he had the most beautiful painting in the world, and after taking you where it was should insist on having your eyes shut, you would likely suspect either that he had no painting or that it was some pitiable dog. Should he tell you that he was a most excellent performer on the violin and yet refused to play unless your ears were stopped, you would say, to say the least of it, that he had an odd way of convincing you of his musical ability? But would his conduct be any more wonderful than that of a religionist who asked that before examining his greed you will have kindness to throw away your reason? The first gentleman says, keep your eyes shut, my picture will bear everything but being seen. Keep your ears stopped, my music objects to nothing but being heard.  So far as I am concerned I most cheerfully admit that most Christians are honest, most ministers sincere. We do not attack them, we attack their creed, we accord to them the same rights that we ask for ourselves. We believe that their doctrines are hurtful, we believe that that frightful text he that believes shall be saved and he that believeth not shall be damned has covered the earth with blood. It has filled the heart with arrogance, cruelty and murder.  It has poisoned the springs of learning, misdirected the energies of the world, filled all countries with want, housed the people in hovels, fed them with famine. But for the efforts of a few brave infidels it would have taken the world back to the midnight of barbarism and left the heavens without a star. The maligners of pain say that he had no right to attack this doctrine because he was unacquainted with dead languages, and for this reason it was a piece of pure impudence in him to investigate the scriptures. Is it necessary to understand Hebrew in order to know that cruelty is not a virtue? That murder is inconsistent with infinite goodness? And that eternal punishment can be inflicted upon man only by an eternal fiend? Is it really essential to conjugate the Greek verbs before you can make up your mind as to the probability of dead people getting out of their graves? Must one be versed in Latin before he is entitled to express his opinion on the genuineness of a pretended revelation from God? Common sense belongs exclusively to no tongue. Logic is not confined to nor has it been buried with the dead languages. Pain attacked the Bible as it is translated. If the translation is wrong, let its defenders correct it. The Christianity of Pain's Day is not the Christianity of our time. There has been a great improvement since then. One hundred and fifty years ago the foremost preachers of our time would have perished at the stake. A universalist would have been torn in pieces in England, Scotland, and America. Unitarians would have found themselves in the stocks pelted by the rabble of dead cats, after which their ears would have been cut off, their tongues bored, and their foreheads branded. Less than one hundred and fifty years ago the following law was enforced in Maryland. Be it enacted by the right honourable, the Lord proprietor, buy in with the advice and consent of his lordship's governor and the upper and lower houses of the assembly, and the authority of the same, that of any person shall hereafter within this province, winningly, maliciously, and advisedly by writing or speaking, blaspheme or cursed guide, or deny our Saviour Jesus Christ to be the Son of God, or shall deny the Holy Trinity the Father, Son, and Holy Ghost, or the Godhead of any of the three persons, or the unity of the Godhead, or shall utter any profane words concerning the Holy Trinity, or any of the persons thereof, and shall therefore be convict by verdict, shall for the first offense be bored through the tongue, and find twenty pounds to be levied of his body. And for the second offense the offender shall be stigmatized by burning in the forehead with the letter B and find forty pounds, and that for the third offense the offender shall suffer death without the benefit of clergy. The strange thing about this law is that it has never been repealed, and is still enforced in the District of Columbia. Laws like this were enforced in most of the colonies and in all countries where the church had power. In the Old Testament the death penalty is attached to hundreds of offensives. It has been the same in all Christian countries. Today it civilized governments that death penalty is attached only to murder and treason, and in some it has been entirely abolished.   In Scotland the Kirk was at the summit of its power. It was a full sister of the Spanish Inquisition. It waged war upon human nature. It was the enemy of happiness, the hater of joy, and the despiser of religious liberty. It taught parents to murder their children rather than to allow them to propagate error. If the mother held opinions of which the infamous Kirk disapproved her children were taken from her arms, the babe from her very bosom and she was not allowed to see them or to write them a word. It would not allow shipwrecked sailors to be rescued from drowning on Sunday. It sought to annihilate pleasure, to pollute the heart by filling it with religious cruelty and gloom, and to change mankind into a vast whore of pious heartless fiends. One of the most famous scotch-divines said, the Kirk holds that religious toleration is not far from blasphemy. And this same scotch Kirk denounced beyond measure the man who had the moral the world is my country and to do good my religion. And this same Kirk abhorred the man who said any system of religion that shocks the mind of a child cannot be a true system. At that time nothing so delighted the church as the beauties of endless torment and listening to the weak wailings of damned infants struggling in the slimy coils and poison folds of the worm that never dies. About the beginning of the 19th century a boy by the name of Thomas Aikenhead was indicted and tried at Edinburgh for having denied the inspiration of the scriptures, and for having on several occasions when cold wished himself in hell that he might get warm. Notwithstanding the poor boy recanted and begged for mercy he was found guilty and hanged. His body was thrown in a hole at the foot of the scaffold and covered with stones. Prosecutions and executions like this were common in every Christian country, and all of them were based on the belief that an intellectual conviction is a crime. No wonder the church hated and reduced to the author of the text. England was filled with the Puritan gloom and episcopal ceremony. All religious conceptions were of the grossest nature. The ideas of crazy fanatics and extravagant poets were taken as solar facts. Milton had clothed Christianity in the soiled and faded finery of the gods had added to the story of Christ the fables of mythology. The church the most outrageously material ideas of the deity. He turned all the angels into soldiers made heaven a battlefield put Christ in uniform and described God as a militia general. His works were considered by the Protestants nearly as sacred as the Bible itself and the imagination of the people was thoroughly polluted by the horrible imagery, the sublime absurdity of the blind Milton.  The judgment day was expected books of account would be opened. Every man would hear the charges against him red. God was supposed to sit on a golden throne surrounded by the tallest angels with harps in their hands and crowns on their heads. The goats would be thrust into eternal fire on the left and stopped sheep on the right were to gamble on sunny slopes forever and forever. The nation was profoundly ignorant and consequently extremely religious so far as belief was concerned. In Europe liberty was lying chained in the inquisition her white bosom stained with blood. In the new world the appearance had been hanging and burning in the name of God and selling white Quaker children into slavery in the name of Christ who said suffer little children to come unto me. Under such conditions progress was impossible. Someone had to lead the way. The church is and always has been incapable of forward movement. Religion always looks back. The church has already reduced Spain to a guitar Italy to a hand organ and Ireland to exile. Someone not connected with their church had to attack the monster that was eating out the heart of the world. Someone had to sacrifice himself for the good of all. The people were in the most abject slavery. Their manhood had been taken from them by pomp and by pageantry and power. Progress is born of doubt and inquiry. The church never doubts, never inquires. To doubt is heresy to inquire is to admit that you do not know. The church does neither.  From that blow the church never can recover.  The church was all powerful and although divided into many sex would instantly unite to repel a common foe. Pain struck the first grand blow. The age of reason did more to undermine the power of the Protestant church than all other books then known. It furnished an immense amount of food for thought. It was written for the average mind and as a straightforward, honest fellow and of the Christian system. Pain did not falter from the first page to the last. He gives you his candid thought and candid thoughts are always valuable. The age of reason has liberalized us all. It put arguments in the mouths of the people. It put the church on the defensive. It enabled somebody in every village to corner the person. It made the world wiser and the church better. It took power from the pulpit and divided it among the pews. Just in proportion that the human race has advanced, the church has lost power. There is no exception to this rule. No nation ever materially advanced that held strictly to the religion of its founders. No nation ever gave itself wholly to the control of the church without losing power, its honor and existence. Every church pretends to have found the exact truth. This is the end of progress. Why pursue that which you have? Why investigate when you know? Every creed is a rock in running water. Humanity sweeps by it. Every creed cries to the universe HALT!  The ignorant are not satisfied with what can be demonstrated. Science is too slow for them and so they invent creeds. They demand completeness. A sublime segment, a grand fragment are of no value to them.  In music they want a melody with a recurring accent at measured periods. In religion they insist upon immediate answers to the questions of creation and destiny. The alpha and omega of all things must be the alphabet of their superstition. A religion that can answer every question and guess every conundrum is, in their estimation, worse than worthless. They desire a kind of theological dictionary, a religious ready reckoner, together with guideboards at all crossings and turns. They mistake impudence for authority, solemnity for wisdom and bathos for inspiration. The beginning and the end are what they demand. The grand flight of the ego is nothing to them. They want the nest in which he was hatched and especially the dry limb upon which he roosts. Anything that can be learned is hardly worth knowing. The present is considered of no value in itself. Happiness must not be expected this side of the clouds and can only be obtained by self-denial and faith, not self-denial for the good of others but for the salvation of your own sweet self. Pain deny the authority of Bibles and Greeds.  I challenge the world to show that Thomas Paine ever wrote one line, one word in favor of tyranny in favor of immorality. One line, one word against what he believed to be for the highest and best interest of mankind. One line, one word against justice, charity or liberty and yet he has been pursued as though he had been a fiend from hell. His memory has been executed as though he had murdered some Uriah for his wife driven some Hagar into the desert to starve with his child upon her bosom. Defiled his own daughters ripped open with the sword the sweet bodies of loving and innocent women advised one brother to assassinate another kept a harem with wives and three hundred concubines or had persecuted Christians even unto strange cities. The church has pursued Paine to deter others. No effort has been made at any age of the world spared to crush out opposition. The church used painting music and architecture simply to degrade mankind but there are men that nothing can awe and at all times brave spirits that dared even the gods. Some proud head has always been above the waves in every age some deogenes has sacrificed to all the gods. True genius never cowers and there is always some Samson feeling for the pillars of authority. Cathedrals and domes and chimes and chants temples frescoed and groined and carved and gilded with gold altars and tapers and paintings of virgin and babe censor and chalice chesapeul patin and ald organs and anthems and incense rising to the winged and blessed manniple, ammest and stole crosses and croziers tiaras and crowns mitres and missiles and masses rosaries relics and robes martyrs and saints and windows stained as with the blood of Christ never, never for one moment awed the brave proud spirit of the infidel. He knew that all the pomp and glitter had been purchased with liberty that priceless jewel of the soul. In looking at the cathedral he remembered the dungeon. The music of the organ was not loud enough to drown the clank of fetters. He could not forget that the taper had lighted the faggot. He knew that the cross adorned the hilt of the sword and so for others worshipped he wept and scorned. The doubter, the investigator the infidel have been the saviors of liberty. This truth is beginning to be realized and the truly intellectual are honoring the brave thinkers of the past. But the church is as unforgiving as ever and still wonders why any infidel should be wicked enough to endeavor to destroy her power. I will tell the church why. You have imprisoned the human mind. You have been the enemy of liberty. You have burned us at the steak wasted us upon slow fires torn our flesh with iron. You have covered us with chains, created us as outcasts. You have filled the world with fear. You have taken our wives and children from our arms. You have confiscated our property. You have denied us the right to testify in courts of justice. You have branded us with infamy. You have torn out our tongues. You have refused us burial in the name of your religion. You have robbed us of every right. And after having inflicted upon us every evil that can be inflicted in this world.  Can you wonder that we hate your doctrines? That we despise your creeds? That we feel proud to know that we are beyond your power? That we are free in spite of you? That we can express our honest thought and that the whole world is grandly rising into the blessed light? Can you wonder that we point with pride to the fact that infidelity has ever been found battling the rights of man for the liberty of conscience and for the happiness of all? Can you wonder that we are proud to know that we have always been disciples of reason and soldiers of freedom? That we have denounced tyranny and superstition and have kept our hands unstained with human blood? We deny that religion is the end or object of this life. When it is so considered, it becomes destructive of happiness, the real end of life. It becomes a hydra-headed monster, reaching in terrible quarrels from the heaven and thrusting its thousand fangs into the bleeding, quivering hearts of men. It devours their substance, builds palaces for God who dwells not in temples made with hands, and allows his children to die in temples. It fills the earth with mourning, heaven with hatred, the present with fear, and all the future with despair. Virtue is a subordination of the passions to the intellect. It is to act in accordance with your highest convictions. It does not consist in believing, but in doing. This is the sublime truth the infidels of all ages have uttered. They have handed the torch from one to the other through all the years that have fled. Upon the altar of reason they have kept the sacred fire and through the long midnight of faith they fed the divine flame. Infidelity is liberty. All religion is slavery.  We do not want creeds. We want knowledge. We want happiness. And yet we are told by the church that we have accomplished nothing, that we are simply destroyers that we tear down without building again. Is it nothing to free mankind? Is it nothing to civilize mankind? Is it nothing to fill the world with light with discovery, with science? Is it nothing to dignify man and exalt the intellect? Is it nothing to gulp your way into the dreary prisons, the damp and dropping dungeons, the dark and silent cells of superstition, where the souls of men are chained by the shadows of stone? To greet them like a ray of light like the song of a bird, the murmur of a stream, to see the dull eyes open and go slowly bright? To feel yourself grasped by the shrunken and unused hands, and hear yourself thanked by a strange and hollow voice? Is it nothing to conduct these souls gradually into the blessed light to let them see again the happy fields, the sweet green earth and hear the everlasting music of the waves? Is it nothing to make men wipe the dust from their swollen knees, the tears from their blanched and furrowed cheeks? Is it a small thing to rieve the heavens of an insatiate monster and ride upon the eternal dome glaring with stars the grand word? Freedom? Is it a small thing to quench the flames of hell with the holy tears of pity? To unbind the martyr from the stake, break all the chains, put out the fires of civil war, stay the sword of the phonetic and tear the bloody hands of the church from the white throat of science? Is it a small thing truly free to destroy the dogmas of ignorance, prejudice and power, the poison fables of superstition and drive from the beautiful face of the earth the fiend of fear? It does seem as though the most zealous Christian must at times entertain some doubt as to the divine origin of his religion. For eighteen hundred years the doctrine has been preached for more than a thousand years the church had to a great extent the control of the civilized world and what has been a result? Are the Christian nations patterns of charity and forbearance? On the contrary their principal business is to destroy each other more than five millions of Christians are trained educated and grilled to murder their fellow Christians Every nation is groaning under a vast debt incurred in carrying on war against other Christians or defending itself from Christian assault. The world is covered with forts to protect Christians from Christians and every sea is covered with iron monsters ready to blow Christian brains into eternal froth. Millions upon millions are annually expended in the effort to construct still more deadly and terrible engines of death industry is crippled honest toil is robbed and even vagary is taxed to defray the expense of Christian warfare There must be some other way to perform this world we have tried creed and dogma and fable and they have failed and they have failed in all the nations dead the people perish for the lack of knowledge nothing but education scientific education can benefit mankind we must find out the laws of nature and conform to them we need free bodies and free minds free labor and free thought chainless hands and endless brains free labor will give us wealth free thought will give us truth we need men with moral courage to speak and write their real thoughts and to stand by their convictions even to the very death we need have no fear of being too radical the future will verify all grand and brave predictions pain was splendidly advanced of his time but he was orthodox compared with the integrals of today science the great iconoclast has been busy since 1809 and by the highway of progress are the broken images of the past on every hand the people advance the vicar of god has been pushed from the throne of caesars and upon the roofs of the beautiful city falls once more the shadow of the eagle all has been accomplished by the heroic few the men of science have explored heaven and earth and with infinite patients have furnished the facts brave thinkers have used them the gloomy caverns of superstition have been transformed into temples of thought and the demons of the past today science took a handful of sand constructed a telescope and with it explored the starry depths of heaven science rested from the gods their thunderbolts and now the electric spark freighted with thought and love flashes under all the waves of the sea science took a tear from the cheek of unpaid labor converted it into steam created a giant that turns with tireless arms the countless wheels of toil thomas pain was one of the intellectual heroes one of the men to whom we are indebted his name is associated forever with the great republic as long as free government exists he will be remembered admired and honored he lived a long boring and useful life the world is better for his having lived for the sake of truth he accepted hatred and reproach for his portion he ate the bitter bread of sorrow his friends were untrue to him because he was true to himself and true to them he lost the respect of what is called society but kept his own his life is what the world calls failure and what history calls success if you love your fellow man more than self is goodness thomas pain was good if to be in advance of your time to be a pioneer in the direction of right is greatness thomas pain was great if to avow your principles and discharge your duty in the presence of death is heroic thomas pain was a hero at the age of 73 death touched his tired heart he died in the land his genius defended under the flag he gave to the skies slander cannot touch him now hatred cannot reach him more he sleeps in the sanctuary of the tomb beneath the quiet of the stars a few more years a few more brave men a few more rays of light and mankind will venerate the memory of him who said any system of religion that shocks the mind of a child cannot be a true system the world is my country and to do good my religion end of section 3 king or so on thomas pain


Well, I want to consult with you about the problem that faces in Central America for three years, and I include the last year of previous administration of the United States that's been trying to stop the advance of communism in Central America by dealing with Americans who invest instinctively and that is supporting democracy. And the reaffirmation of democracy in Costa Rica I think has been evident to all of us in the transition from military rule to the elected civilian government in Honduras and the launching of democracy in El Salvador with the success of elections on last March and it demonstrates today around the right course. So the good news is that the Marxist Revolution is inevitable in Central America. The bad news is that it cannot yet be ruled out. The military capability of the guerrillas let me stress the military capability. For we're not dealing with professing irregularities but with a train of military force. They kept the government from all political and economic projects all the way it could be made. I've sent the reason for this and the availability of training, tactical guidance and military supplies that are coming into El Salvador around the world. Tons of ammunition are being flown in from Nicaragua and on our side the continuing resolution we have has led to a liberal security assessment for El Salvador this year that's under the law last year and below what we've discussed for 1984. And this is just not enough in this critical moment of their battle for democracy. The Constitution is being written there president-elected. Potential elections are being prepared and the peace commissions just given a mandate to finding ways to bring as many Salvadorans as possible into the democratic process including many of those who are out there in the jungle fighting. We've been studying how we can help them help themselves. Economic reform needs time to work. Democracy must be nurtured. The problem today is that the military strategy of the pro-democratarians is proving devastating to our democratic friends. Military assistance is vital to give the democracy a chance. Yes, many of the people missing a card here I'm sure you know I'm not talking about that when I say military assistance about combat. Military assistance is not a complete solution. In fact, the early passage of trade and investment provisions of the Caribbean initiative is every bit as important. Our friends must know that we'll never abandon them and that we will pursue our colon effort to foster economic development and freedom. This means continuing to score all the possibilities and reconciliation for peace. And if we allow the government to transform itself into democracy maybe not as fast as we'd like but is reformed if we allow it to be knocked off by the guerrillas who don't have the people with them that was made evident during that election then no government on the Isthmus will be safe. We can't permit this. Half of our trade goes through the Caribbean. We depend on the security of the canal. We cannot accommodate thousands, yes, millions of people who would flee this integrating sector now. Us as the target for them. We must win the elections. We've been exploring ways to help what is needed there. And I'll sell the door to most of you. I've asked George and other senior officials to consult with you over this week ways that we can work together. I hope they can meet again next week and set a common course right now before trying to George to make sure you get her what's going on. I'd like to call for a few words on Jean Griffith because she'll just return.


You need a financial advisor with the freedom to focus on your specific needs. Whatever your goals, Reeve Potter can create a game plan tailored to you. Call Reeve at 432-0777 at Pikeville, Kentucky to learn more. Norton, Virginia will be hosting the sixth annual High Knob Music Festival Saturday, June 18th at the High Knob Recreation Area. The festival will feature food vendors, six bands, and a flag folding ceremony. What's kind of unique about our festival is that everybody that lives here in southwest Virginia, anybody that's visited southwest Virginia, one of the first places they want to go back to is up on top of the mountain. And there's several different places that people go to as far as Benches Rock, the Flag Rock, the Observation Tower, and one of the places that everybody wants to go to is the High Knob Recreation Area, and that is the home of the High Knob Music Festival. The festival is free to attend, however, the George Washington and Jefferson National Forest does charge a $5 entry fee. High Knob has asked that those attending the festival bring three cans of food to be donated to the Norton Food Bank on behalf of all the festival goers. It was just a group of friends that got together that wanted to do something special for the community, and it really has evolved. You know, we first started off by wanting to do a music festival, now we've kind of taken over the caretaker ship of the park. In addition to hosting the festival, the High Knob Festival Committee has made large improvements to the amphitheater stage and electrical system. The thing that we've been doing up there is, you know, and our event is one day a year, but our main goal was to upgrade the facility so that anybody that wanted to go and utilize the park could go up there and they could, you know, have an ample amount of supply of power in a nice stage to perform on. For more information on the High Knob Music Festival, go to High Knob Music Festival on Facebook. For Mountain Top News, I'm Brianna Robinson.