Thank you for that kind introduction, and greetings to several of you in the audience whom I know in the practicing community here of ophthalmology in Washington. It's actually a very vigorous and vital dynamic practice of eye and vision care. I'd like to spend a few moments this morning talking about orthomic genetics and actually what is now happening in the application of that to care. Let's see if this works. There it goes. Some presentation objectives. I will briefly review some of the history of where genetics has come from historically. And you will by the end of this be seeing a number of ophthalmic photos of various eye diseases, the phenotypes, and then to consider where ophthalmology is going to be incorporating gene discovery in therapeutics. Eye disease in a big hospital like this at Suburban may not seem to have center stage, but in fact, the eye disorders collectively rank in the top 10 of the maladies that affect us as humans according to WHO just a few years ago. Obviously we see eyes all the time. I'm looking at a lot of eyes looking at me. And you see yourself in the mirror in the morning. And when you're looking at the eye, you're looking at the external anterior segment, the eyelids, pupils, sclera, iris, but hidden at the back inside are some vital elements of vision. The neural retinal tissue, the red lining here at the back. Red because of the molecule that is light sensitive, rhodopsin. At the center of the action, the macula, and you're looking at the slide with your macula, it's the fine focus center of vision. There are several major diseases here. We see three of the four major diseases of the eye cataract. A lot of cataracts surgeries are going to be done in the Bethesda and Washington community today. And glaucoma. Glaucoma straddles the front of the eye, where pressure can build up because of an outflow, obstruction of fluid, and that pressure for reasons that are rather indecipherable still at the moment ultimately affects the optic nerve which contains the axons of the 100 million rod and cone photoreceptors in the retina. And then macular degeneration, which is the scourge of vision. What is not shown here is diabetic retinopathy, the effect of diabetes on the major blood vessels that line the back of the eye. But that's the way we look at the eye when I was a resident 30 some years ago. Now we look at the eye as tissues and cells. All of these cells, the light sensitive rod and cone photoreceptors, the rods containing that radopsin that imparts the reddish color to the retina. And the cones which come in three flavors, red, green, and blue, and give us the full spectrum, chromatic spectrum of vision that we all enjoy. Now medicine is moving to cells. These cells have obviously been there a long time in the textbooks, but now we're actually dealing with these on a rather medically personal level. And I'm going to tell you some stories about rod and cone photoreceptors. But back on the thread of genetics in general in eye disease, here are six photographs. These are the kinds of patients who will be seen in the Washington community today. Individuals with cataract. This is a particular special cataract. You can see these white puntate dots, the cerulean cataract. This young child with the one eye is looking right straight at you, but with the other eye is rather askew, strabismus, muscle surgery. Pediatric ophthalmology. The front here, the iris looks good until you can see that it's not attached at the base. There's a dehissence, an iris coloboma, a developmental issue. And at the bottom, three views of the back of the eye. Age-related macular degeneration, a sheet of blood on the back of the eye. Through which vision is going to be distorted and when this blood consolidates and tears up the neural retinal tissue, obviously the vision is going to be the impaired significantly or glaucoma. The enlarged yellowish center missing the axons because of elevated pressure in the eye. And macular degeneration of the Stargardt flavor. Dr. Stargardt, German, two centuries ago. An overt genetic problem of vision. But in fact, all of these have a genetic issue going on. So the public health impact of all of this vision impairment is considerable. Tens of millions of our fellow citizens suffer visual impairment due to diseases that have either a direct genetic basis or result in part from genetic risk. And as we have birthdays every year, the incidence of age-related eye diseases is increasing at an obviously large cost to us as individuals and to society. So while eye care is well advanced, in fact we need to have more effective therapies. Let me just tell you how I'm going to be using words today. Genes, genetics, genomics, and medicine. They flow together. Genes, the biologic code. Genetics, the play out of those genes, let's say in families. Inheritance in families and ultimately affecting society. Genomics, how the gene product, the product that the gene makes. Affect cells and ultimately what the mechanisms of cell processes are and how that plays out in disease and medicine, the treatment of disease. That's what we and you will be doing here today at Suburban. And what we have seen is that we started with genes and we're now squarely in the camp of medicine. But let's roll the clock back two and a half millennia. Hippocrates, blue eyes are inherited. That's an interesting idea. Or speaking in Greek, so I'm translating. Squinty-eyed children have squinty-eyed parents. When a nearsighted person squints through narrowed eyelids, you perceive a little bit better. And if you look at the kids who are nearsighted, you will find that quite frequently the parents were nearsighted. Or Aristotle, 50 years later, further described myopia. And he recognized that blindness can be transmitted between parent and child. And that was an idea picked up later on by Plotarchus. Speaking of the biblical Isaac and Jacob, both of whom had older age vision loss. And he had the concept of hereditary old age blindness. It was that macular degeneration. Now speeding up the clock and going back to 1770, Lorton Dalton recognized that color deficiency runs in families. And it is us poor, feeble men who suffer it as opposed to women. That's because the color genes are on the X chromosome and men have only one. Whereas women have two X chromosomes. And when the men have the color deficiency on one, there's nothing to mask it. Whereas the women have a second copy that usually has a normal color gene on it. And then a century later, Horner recognized that quite frequently men who were colorblind had uncles, mothers, brothers who were colorblind, speaking of X chromosome inheritance. And then going a century further, just a few decades ago, Jeremy Nathan's cloned one of the genes that imparts light sensitivity and ultimately color vision, not with Riddopsin but with the coloropsin genes, Riddopsin and the coloropsins. So if we look at that year 1983, when Riddopsin was cloned, there were very few genes that were captured. But across the three decades span, the vision community has been extraordinarily vigorous in identifying genes related to eye disease. And now there are some 600 genes that are known, 200 that affect the retina, nearly 200, 150, 200 that are affecting the lens and the cornea at the front of the eye. The eye turns out to be, unfortunately, very rich in monogenic traits in which a single gene causes a vision problem. In fact, still about 20% of the identified human disease genes involve the eye and vision. So when we have all of these hundreds and hundreds of genes, what difference does it make? Well, we, we, Medicine, Science, Vision, Research, we are now imparting on the new frontier of addressing these problems at the gene level. In a moment I'll tell you about RP65, a molecule that causes LCA, Labor Congenital Amorosis. But let me defer that for a moment. In this case, however, that there is a defective gene, actually both copies, both alleles of the gene are defective. And by providing an external normal copy, one can restore the cellular function that depends on RP65. Or in the case of parent to child direct transmission, a dominant transmission, one may, in fact in animals you can, but in humans may be able to suppress that one copy that's defective and allow the second normal copy to function throughout life and retain vision. So you'd have to suppress the mutant gene or repair it or just go around the whole system, don't worry about the gene, but deliver some other product that is therapeutic. Let me turn back to this RP65 for a moment. The story starts in 1869 when Dr. Theodore Labor saw several children who were blind, they were born blind, severe vision loss, they had bobbing eyes, nystagmus movements, a sign of congenital severely impaired vision. And a century later when the electroretinogram was invented or identified, used that the responses were found to be non detectable. The electroretinogram is similar to the electrocardiogram, but in this case it's for the retina, the neural tissue in the eye. And that tissue was not functioning. These are pictures that I was taught when I was a resident 30 years ago. So you look into the eye and sometimes you see nearly nothing, but the child's not seeing. Other times you look in and you see darker spots of injury pigment from injury to cells in the eye or you see a disillusion, a breaking up of the neural retinal tissue. So this is LCA, labor congenital amaurosis, Dr. Theodore Labor's congenital blindness, LCA. This is LCA, as I was taught it in the premolecular era. This is now LCA, 19 genes and counting. These genes are functioning at the level of the rod and the cone photoreceptors and the supporting tissue called the retinal pigment epithelium. And these 19 genes in fact are playing right here and the one that I'm going to focus on, RP65, is involved in the vitamin A cycle. Eat your carrots, grandma was right, if you don't eat enough carrots you're going to have vision problems because you need vitamin A. And in fact there are enzymes specifically at the back of the eye that process dietary vitamin A and make it available in the proper molecular configuration to function for vision. So let's return to RP65, the molecule, and go about a decade and a half ago, Mike Redmond working just across the street in the laboratory in the National Eye Institute was looking at the genes that are abundant or actually the proteins that are abundant in the retinal pigment epithelium RPE and there was one with a molecular weight of 65 so it gets the name RP65 protein. He cloned the gene for it and everybody admired his technical prowess. He's got a new gene. What does it do? Nobody knew. Five years later Mike knocked out the gene in a mouse and the mouse was blind. So we know that RP65 is critical for vision, rather crude way of finding out but very effective. At the same time in Australia humans were found by a geneticist, humans were found to have mutations in the RP65 gene and they were blind. In fact they had LCA, labor congenital blinds. And then the story moved to Sweden where a dog was found, the Swedish Breard dog was found to have mutations in this gene. And then the story speeded up quite a bit. Here is one of the dogs, a Swedish Breard dog. Actually that's not I'm told a Swedish Breard dog but the gene was put into the dog so that this dog did crossbred etc. But this dog was blind from RP65. And then within a matter of 1998 to 2001 just in the space of a couple of years gene therapy was done to put the normal RP65 gene into this dog and a couple of weeks later you could play frisbee with you. Obviously great story to take down to Congress. Everyone loves dogs, everyone loves genetic stories so he is our best ambassador for vision. Literally Senator Harkin has met him etc. Well looking at the electro retinogram function complex slide but not that difficult. Panel one, two, and three. Middle panel, flat responses, this panel, big waveforms in a normal, in a normal compared to this dog before treatment, no action. This is very dim light and very bright light. A flash of light startles the neurons and gives it these waveforms.  But when you put the gene in, RP65 gene, look what comes back. That's why the dog can play frisbee with you. In fact the dog tells you it's got vision and the electrical function says it has vision. Well from 2001 it was just a major step but only a few years before gene therapy was done for kids who had LCA from RP65. And that was recognized by Science Magazine a year later in 2009 as a seminal event in science and medicine. It was only the runner up. I don't remember what the winner was but I think it should have been the winner. Here is Al McGuire, one of the authors on the first report of treating these kids with blindness. And he is treating a young man injecting the gene into the eye. Let's just look at what that really means to treat an eye genetically. What he is doing here in cartoon is to take a very narrow needle, fine needle and put it through the eye wall underneath the retina. Inject some fluid that contains the vector. Make a little bubble or here another illustration of bubble. Here are the rod and cone photoreceptors. Here is the retinal pigment epithelium where the gene resides. So he puts the fluid next to those RPE cells, provides the gene ultimately and this child is now playing baseball. Well this is, that was RP65, one example of gene therapy for vision. And there are many others. Stargardt macular degeneration I mentioned that showed you a slide right at the outset. Dr. Stargardt, we know the gene it's ABCA4 and there is a company Oxford Biomedical which is quite vigorous in working in gene therapy. In this case they are using lentivirus because this gene our ABCA4 is a monster. It's huge. It has nearly 60, 60 exons. It's a big, big gene. It doesn't fit in most delivery vectors. So you turn to something that can carry a big cargo, the lentivirus. And they have a trial going on. Starrgen just started recently. Here's another one, Usher syndrome. Children born deaf and rapidly going blind such that by age 20 they really have negligible residual vision. Also a big gene. And they have a trial going on for Usher syndrome. Or, and these are direct, these are direct gene therapy, these two, these two trials. Or somewhat indirectly using the same delivery, the lentivirus, but delivering therapeutic vectors, therapeutic molecules, endostatin and angiostatin, delivering the gene that makes the protein and the protein rescues the function of macular degeneration diabetic retinopathy causing new blood vessels, neo vascularization of the retinone. And in aggregate the vision community is quite vigorous in working in the area of gene therapy. Labor congenital amaurosis, RP-65, start of the ball rolling. Here's Usher syndrome and Starrgarts, soluble flit. Many of these currently are being done in outside the U.S. But we expect that they will be moving here into the states soon. What else do you do with genes? You've got genes. What do you do with them? Well, how about using them for medicine to inform people of their fate? Here is an interesting story that I would commend to you, New York Times, July 9, last summer. And this is for ocular melanoma. You can read it online. Cassandra Catten, age 18, noticed a vision problem, went to her ophthalmologist who said, Cassandra, you've got a problem. You've got a tumor. You've got a cancer in your eye. It's growing. It's broken up the retinone. We're going to have to do something. In this case, the doing something literally is to remove the eye and nucleate the eye. Because you can't contain this cancer. You take it out at the source, take the eye out, put in a prosthetic shell so that cosmetically you and I wouldn't notice. But obviously you're losing an eye, Cassandra. Well, ocular melanoma, melanoma, skin melanoma, it's a pigment cell condition. So it is the pigmented uveal tissues of the eye. Here at the front of the eye, the iris has a pigmented tissue. And you can see the iris melanoma kind of fluffy, elevated. It's a growth on the iris. Bad, bad, bad sign. That eye is in serious jeopardy. Or looking at the back of the eye here is a tumor, a melanoma, a ball of melanoma growing underneath the retinone. About 2000 Americans will be newly diagnosed this year. And half of them are going to die from metastases. But the story becomes extremely interesting for these patients. But also for all of cancer, by the work of an ophthalmologist, Bill Harbour, working at Washington University St. Louis, who collected these cases and began to do proteomics on them. And sorted out the cases as people who didn't die and people who did die and compared those, and came up with a critical difference. People who died, he found had mutations, an alteration of the BAP1 gene in 84% of those metastatic tumors. BAP1, breast cancer, BRCA1, associated protein 1. And his findings suggested that BAP1 suppresses metastases. And so if you, it's a negative, double negative statement. If you make mutations in this, you cause metastases. So if we, and this paper published in 2010 was rapidly turned into a medical diagnostics test by Castle of Biosciences in 2011. And you can order it here in suburban. Turning back to Cassandra, the question now is which class is she?  And this is a composite of several hundred cases of oculomelanoma. Or is she in Class 2 with a median survival of just over four years? It turns out, read it online, she has Class 1, she's all set. But the second part of that same story is another individual who falls in this class. That is medicine, folks. You can't always fix things, as all of us know. But you have to work with patients and give them information that they can act on. And I think this is first class medicine. Well, what about this rumor that people don't want to know what they've got? Let's stick our heads in the sand. Don't think so. People want to know about the genetics in their family. These, I make a joke, are two of my favorite magazines. And in one year, 2007, science has human genetic variation, breakthrough of the year. And Wired Magazine says your life decoded. People are very interested in their genetic status. So how does ophthalmology deal with this? We've got 600 genes to deal with. And we're just scratching the surface. How do we deliver on the promise of diagnostics and genetics for people at a time when opportunities are expanding? How do we handle a large variety of these infrequent monogenic diseases in which one gene is converted into a disease? Several years ago, the I Institute initiated a project called I-Gene. Because several years ago, there were boutique laboratories, research laboratories that were doing genetics for one or two genes. If you are interested, just go back to your computer and Google I-Gene. And this will come up so you can get the information yourself and participate if you wish. It's a national network of these boutique laboratories that in aggregate are testing 35 genes, excuse me, about 100 genes for 35 diseases. And the scheme here, this is under the National I Institute. So our scheme is, yes, it's important to provide diagnostics to people and genetic information, but it's also critical for research to know the medical characteristics of those people. This slide breaks out into three parts. The patient and the physician, part one, sends a sample to coordinating center in Kerry. I see you sitting there. Kerry, raise your hand. Kerry is running that right across the street. And the center sends it, distributes a sample to one of many laboratories that are boutique research laboratories at the moment. They've got special expertise in your gene, if that's what you need. The information comes back, goes back to the patient. That's medical care. At the same time, the individual signs a consent right up front that says, anonymize my information, keep it safe, but use it. Use it for research so that we can understand what these diseases are and how to proceed. So we've got a unified medical care research venture going. We've got, has a registry, consent, contact information, the phenotypes, meaning the medical characteristics, the genotypes, the gene level, and a repository of samples. It has been well received across the country. All but five states have participating sites. I keep telling Kerry to take a site visit to Vermont to encourage them. She wants to go to Hawaii and Alaska instead. And we're enrolling about a thousand patients a year. I think, Kerry, that's your saturation point. A lot of hands-on work, but the importance is to couple what happens in this hospital, the medical venture of patient and physician, medicine, to get that information put together with the genotypes so that we can move on with understanding the interplay between phenotypes and genotypes. Diagnostics is moving on, as we all know. Now we're at the level of sequencing the entire human genome for individual patients, and particularly with suburban couple to Johns Hopkins. This is state-of-the-art medical care. It's tricky because the information is so vast, 20,000 genes you're looking at or something. The information is so vast that it becomes an analytics problem and not a cost of sequencing problem. The cost has dropped over the past six, seven years from a million dollars for your genome to a thousand dollars for your genome. That's not the cost. The cost is the analytics and the medical information to extract from that. Ophthalmology has been front and center in this. This is a page 2010 science magazine, affordable exomes fill gap in rare diseases. Yes, a lot of our diseases are rare diseases, whether they're cardiology diseases or ocular diseases. In this case, what was featured was the Litsky family, Betty and Carlos, four wonderful kids born with vision, no problem. Unfortunately, three of them are now blind. And despite all of these boutique laboratories in vision looking for this gene in the Litsky family living in Miami, it was elusive until a group just shotgun the human genome in this family and came up with a new gene, DHDDS. It turns out to be an enzyme that put sugar groups on the rhodopsin molecule and the rhodopsin molecule I mentioned was cloned by German Athens in 1983. And without those sugar groups, the rhodopsin molecule, the light sensitive molecule of the eye doesn't function and so the kids lose their vision. And now therapy ideas are moving forward in animals for DHDDS. So far, I have spoken only of these single gene causes you the problem diseases, single gene diseases, monogenic diseases, Mendelian, Gregor Mendel diseases. But there's a whole world of patients seen in this building who have what are called complex genetic diseases. In general, these are the most common that affect us. And they are due to risk factors that ultimately impair together collectively impair cell function and cause disease to happen. Most common of those blinding conditions for ophthalmology is age related macular degeneration AMD. And at the bottom, what was unfolding was a panoply of pictures and normal fundus, the optic nerve, the blood vessels, the macula, the reddish retinal tissue. And with aging, a number of individuals develop these spots, their lipid accumulations, their debris accumulations, they're called drusen. And those drusen predispose, heavily predispose to one of two things, either atrophy, death of tissue or hemorrhage. And for either of those, when you have this in the center of your vision, you can't see through it. You are blind, legally blind at least 2200 from loss of central vision. You've got your peripheral vision, you can get around. But you can't drive, you can't play cards, you can't watch TV, you can't read. Two million Americans are already legally blind from AMD. Many more are at risk, and we're all getting older. So let's get on with the show and do something about it. But this is a complex disease. There's no single gene to be looking for. You've got to look for the risk conveyed by a gene. And in fact, well, here's just an illustration of cartoon form of havoc this causes with vision. And then a seminal event happened just a few years ago, 2005, when five groups simultaneously identified the CFH gene, complement factor H gene. Just parenthetically, I love being part of the vision community. We don't do it one time, we do it five times. You worried about, is this report true or not? Well, this article of this issue of science has three independent groups publishing the same gene, identifying the same gene for AMD. And I would congratulate Emily Chu sitting here, who with Rick Ferris and John Paul Sanjuvani at the I Institute were front and center in the Klein article of CFH gene. So what does this tell us? It's only a gene. Well, this tells us a lot. This is the complement cascade system, the immune system of the body. And within a year, two more complement components, factor B and complement component C2 came on the scene, more risk factors for AMD. This says that AMD is a cousin of other chronic diseases that have a play with the immune system, Alzheimer's, Parkinson's, cardiovascular disease. These are cousin diseases in invoking the surveillance mechanisms of the body. And quite remarkably, if you add up these three genes, 74% of the risk of developing AMD is accounted for. These are heavy big players. Here is a schematic, simplified schematic of the complement cascade system. CFH sitting in the middle plays in all three pathways. Here is C2, here is C7, here is factor B. So AMD is somehow invoking activity of the immune system. And obviously, that last slide gives us some therapeutic targets to consider. Well, I'd like to roll the clock back to 2005 for just a minute. Here are the Mendelian single gene monogenic traits. In 2005, there were 1700, and at that point, vision ophthalmology had identified about 450 genes that caused vision problems. In other words, the vision community owned, very strong word, don't mean to imply anything, but contributed a quarter of the cloned disease genes. Whereas the complex traits were poking along here a different scale at fewer than 10. And then AMD came on the scene. It was number eight or nine in diseases for which risk genes had been identified, rather seminal accomplishment 2005. Here it is. This was the only gene identified, only disease gene identified in 2005 for common complex disease. By a year later, 12 months later, here's a second macular degeneration gene. And here we have a cardiovascular problem, prolonged QT interval or inflammatory bowel disease, rare company 2006. 2007, medicine catches up. 2011, oh my goodness, here's the state of medicine. This is now, what, a year and a half ago? 249, 250 medical traits, common complex diseases, 1600 genetic studies. The entire genome is populated with knowledge about the diseases you and I see today at suburban and at NIH. But I don't want to imply, as some people think I do, I don't want to apply that life is merely genetic. It's bad enough to have the complement factor H gene, because that increases your risk of developing AMD fourfold over not having it, or sixfold for another AMD locus. But if you smoke, watch out. That fourfold goes to ninefold, and this sixfold goes to 22. So life is complicated, but a lot of what we deal with is genetic. So how do we find these genes? The first three kind of dropped in our lap. Total surprise to me, Emily, thank you for pursuing this. But how do we find the rest of the genes? The I Institute a few years ago under Haman Chen organized a group, a research group, 24 different research groups, and they pooled their cases, several thousand disease cases, and I didn't schedule it this way, but there was news yesterday that this group, their paper has just been accepted in Nature Genetics to be coming out soon, which will report a total of 17 loci, 17 genes conveying risk for AMD. That takes concerted action. And it's bad enough to remember all those gene names, but the important thing is, those genes begin to cluster. We talked about the cluster in the complement immune system, cascade. Some of the genes cluster in lipoprotein pathways, others in matrix pathways, others in angiogenesis signaling pathways. So now we're getting a flavor of the complexity of AMD. And the I Institute is doing the same thing for glaucoma. Glaucoma has been recalcitrant. No real genes. Yes, there are tigromyacillin gene late night, when was it? 20-some years ago. But other than that, genes have not been found. But getting together a group under auspices of the National I Institute, they just last fall published a whole genome scan, and there were two loci that popped up. So we hope that genes will be found. But actually the lesson on this is kind of curious. This group met three weeks ago, and what they concluded is their clinical input is off base. The genetics is fine, but it's not coming up with things because the clinicians are saying they really don't understand the concept of glaucoma. That's an admission for our clinician, right? But it's an important part of how this field moves forward, to take genetic information or the lack thereof and have it feedback into medicine. So how many genes do we need? Is 17 enough? There's a lot of information that just flashed up here, but let me run this real quickly. If we take those three genes that accounted for about 74% of the risk, the first three major genes, it turns out that we classify 74% of the true cases, but we would miss on 31% of the controls. Not bad. Two to one. The problem is, many, many more people are in this normal group who will not get AMD. So when you do the multiplication and misclassify a huge population, misclassify it one-third of the time, it turns out that in seven of eight people you say are at high risk, you're wrong. That's not a very good test to use. So in fact, you do need a lot of genes and this is going to be a very complicated process in complex diseases. Maybe that's why they're called complex diseases. I'd like to just wrap this up in a few minutes. What's next? Here are some seminal events in medicine. Polio vaccine. Many in the room are old enough to remember the excitement that this generated. And then a decade and a half ago, cloning a mammal. Oh my goodness, the world was going to fall apart. This was seminal. And a decade ago, the Human Genome Project, Francis and Craig Ventner. Seminal events. I'd like to, and they all made well in time and time, but here's a seminal event for ophthalmology. Published Nature a year and a half ago. This, folks, is a mouse eyeball grown in culture from single mouse embryonic stem cells. This is a seminal event. Yoshiki Sasai did this work. We had him speaking across the street last year. He started with mouse embryonic stem cells and they grew into not a monolayer of cells, but in fact, organized a whole organ. The eye. All that's missing is the lens and this thing could see. The eye could see, but how do you connect it to the brain? Well, we've got to figure that out. And when that's figured out, we will be able to grow new eyeballs for people. That's a bold idea. A year ago, I took that idea to the National Advisor Eye Council, the oversight body for the NEI, and said, let's consider being bold. Let's consider being audacious. The Eye Council took that up and they came up with the term audacious goals challenge. This was an aspirational slide a year ago, but it's now reality because two weeks from now, a week from Sunday, two weeks from Sunday at the Bolger Center in Potomac, we will have 200 people comprising all of these disciplines together to think about how to stimulate innovative, visionary thinking to take vision forward. So stay tuned, please, because this will be two weeks from now. Obviously, it takes a little time, but I'm pleased actually that a mere 12 months after proposing the idea, in fact, we're able to act on it with 200 clever thinking innovative scientists getting together to envision the opportunities again. We'd like to be at the edge of current technologies or maybe even beyond where we are. Ten years to make things play out would be our goal, and that's a long time. I don't want to do science fiction, so let's stay in the ballpark, but let's actually think about what we can imagine doing. Can we connect an eyeball grown in a dish into the brain? I have no idea. But if one could, what would be the implications of that kind of thinking? So the Institute will invest a significant part of its resource, our resource, your resource, because it's tax dollars, into thinking the next decade and two decades ahead. Well, that's it. I thank you for your interest, and I think that we are moving ahead, and I think all of medicine is just leaping forward now. This started, one measure is a decade ago, with Francis and others working on that human genome. It has proven to be seminal for medicine, for research, and now for patient care. Thank you. I have a few comments or questions, but obviously, yeah. When you do replacement of genes, is it a one-shot of a therapy, or do you have to have repeated replacements, and is there self-generation, would you give? Well, that's a very interesting question. Could you paraphrase it for us? That's an interesting question. So when you do gene therapy, do you do it one time, or does it take repeated dosing? You can do it one time in most cells, and particularly cells such as a pigment epithelium that don't divide and replicate. The gene goes in, it snuggles next to the chromosome, the genetic elements that are in the cell naturally, and then acts, as though it had been there a long time and it stays there. That is certainly the case so far for the dogs that were treated, our representative to Congress, just died a decade after the therapy and had not lost anything that he had recovered. So it looks like it's a one-shot deal. And actually, buried in that is a seminal problem for the pharmaceutical industry. How do you price it? How do you cure somebody? One shot. How do you price that one shot? Is there a special place that the central nervous system has as a sanctuary away from some of the immune system out in this matter? We think so. The neural tissue, the retina tissue at the back of the eye is relatively protected from immune attack, but it's not actually totally isolated. It is simply, the immune system is slower to act with it. So we're not totally immune, but it does give us a head start. You just snuck that in on me. So do the viruses cause a problem? I thought you were first talking about what's used currently, AAV, adeno-associated virus. It seems AAV seems not to cause a problem. Lente is of greater concern. It's part of the HIV-AIDS axis. And so those lentiviruses are engineered quite specially and specifically to remove elements that might cause cellular proliferation, tumor growth, etc. So far, with the lentiviruses that have been put into the human body, they, therapeutically, they are not causing a problem. I'm sure at some point there will be something that happens. But in general, I think it's a safe statement that prudence, medical prudence, research prudence, can't overcome the problem. Turning that around, the origin of diseases? I'm not a virologist. I would look to Bob Nussinblatt sitting back there quietly, who knows a lot more in answer to your question. In this case, the viruses that are being used are the genome of the virus, codes for some very specific elements. And those elements have been taken out, re-engineered and put back together. So these viruses are disabled historically. Do they cause? Well, they can be. There are examples of genes in the wrong place, or genes from one organism, one species, and another species. And it is thought that they were deposited by a naturally occurring viral vector. So in fact, viruses genetically can cause mischief. Yes. Absolutely. That's the point of it. I would encourage you to go to iGene and you can read a little bit about it. But this is a public database, public in the sense that through research permissions, one gains access to it, one gains access to securely coded information. There's no private information, individual information. But one can and research can drill down to that individual level because of the consensus that are in place. So what about commercial gene testing? Specifically, the question is phrased for common complex diseases and for AMD.  What do you make of it? Talk to Carrie next to you. She'll have the answers. But here's my answer. I showed you the example of the mischief that is caused by imprecise information. The genetic testing that is being done by these services does nothing more than we do. And consequently, they are going to be mislabeling a considerable number of individuals who will not be getting AMD, but think they may because the testing is imprecise. So it's a risky area, difficult area. Could you comment on the process of getting this wonderful science out into the hands of practicing clinicians who are out there slugging it out every day? How is that working? How is it working in the eye world to engage day-to-day practitioners? I am pleased to be an ophthalmologist because I think the ophthalmology community is the best. Oh boy, I shouldn't say that. But it's very good. And ophthalmologists seem to be curious people, people who are curious, and they are incorporating genetic information as rapidly as all of medicine is. Now, one of our strategies with the iGene genetic testing, in fact, was to engage community ophthalmologists. And as that map of the United States all coated green, except for six states, the practice community, in fact, is participating in this. And the American Academy of Ophthalmology meeting every year, like all professional societies, has specific sessions on genetics testing and implications for practice. Do you focus on competencies or basic knowledge or both? It seems to me that quick way to get this engaged, doctors understand how to function with this data rather than knowing which exon. That is a critical, critical issue. And again, I'm going to point to Kerry because she thinks about this, as does her compatriot next door, in how does one use genetic information.  You're seeing a patient with Stargard. What do you do with the information when it comes back? It is going to be necessary for all of medicine to be teaching genetics hard, core genetic knowledge in our medical schools as they are doing. Other comments or questions? Yes. So how do you tailor therapy to the cells and parts of tissues that are in particular need? Well, for the RP-65, the congenital blindness, labor congenital blindness, RP-65LCA disease, that is an enzyme deficiency in the retinal pigment epithelium. So you put the vector right next to the pigment epithelium. You flow the fluid right onto the pigment epithelium in the operating room right here when retinal surgery is done. So you can get the gene in physical proximity to the tissue. Let's say that there's an extraocular muscle problem. It is easy to put a needle to the muscle, deposit some fluid and have it suffuse through the muscle fibers. So in fact, for ophthalmology, for the eye as an organ system, the eye is very amenable to genetic intervention, I would think. Other comments or questions? No, please join me in thanking Dr. Segal for one question.


Rydym yn ddim o'r fath o'r cyfle o gael lluniau arddangos wrth gwrs o'n ddweud yn eu ddweud. Tre'n mynd i'r byth이 bliadau os yw'r ysgfaith dysgu i ddyn nhw'n ymwinell. Dyna'r ystod y ffordd am rhan o'r ddim enwedd chi'n hyfforddiad. Yr ysgrifennu ei wneud i'w cyfnodd y lluniau gyda'r ysgaflwyntion cyfrydAU i gyd yn ymgyrchu a gyrsanaethau. is really that impact assessment is via publications of citations data only. We think that's narrow in the modern world. We think it's a really limited view. There's information which isn't really meeting the needs of funders and universities. And so there's an opportunity to create something broader, more contextual. And so about four years ago I worked a lot with my team and we came up with a vision for the space and we decided that we wanted to democratise data. We wanted to get data out there so that it was more easy to use. We wanted to de-silo data. And the key thing was that we wanted to contextualise search and connect academics with content. Digital science, as some of you may know, is kind of a schizophrenic organisation. We invest in lots of companies with very pretty logos. And we try to bring them together strategically. So we have lots of people who have deep domain expertise in specific areas. And we can bring all those different domain expertise together to meet needs across the research ecosystem. And so publications are still central to what everybody does as they still remain the atom of research communication. But there are all of these other things that one needs to take into account. And as you can see, we didn't start from a standing start four years ago. We actually had companies who were doing bits of the puzzle already. We had created Grid as a CC0 source, which allowed us to look at institutional names. We had Uber Research looking at a grants database. We had Altmetric trying to pull together the attention from the space. And once we had these ideas together, we wanted to obviously socialise them and make sure that we weren't doing something completely useless for the industry. So we went out and we talked to a lot of institutions and over a hundred different academic institutions and funders from around the world joined us to try and make sure that the use cases we were meeting were really relevant. So we created something that we think is quite innovative. What we did was we moved beyond the publication and we brought in grants data, patents data, clinical trials data into a single database. We also wanted to make things openly and freely available. And so we needed to do that with certain specific types of data. So how do we actually build dimensions? Well, at the core of everything that we do, we need to create a data spine that allows us to hook enhanced data into place. And the core of that spine was actually things like PubMed, Crossref, all of these open data. So dimensions is almost a study in what you can do if you have open data available. And so we brought all of these data sources together to create the core of the dimension system. I40C deserves a massive shout out because none of this would have been possible without the work that they've been doing. And we then were working with actually some very generous publishers. I know that that's a phrase that many of you are often here, but publishers who actually worked with us and actually allowed us access to their full text so that we could data mine it and enhance the metadata that we were making available to academic colleagues. And they did that in a way that allows us licences to be quite free with the data and to allow it to be changed and disseminated around the industry. We worked also with grants. We have about 250 funders in the system. That's about 3.7 million grants. It's about $1.3 trillion worth of grant funding data, awarded data, not opportunities data. And about 300 million of that is grants that are currently held or about to be spent. So it's actually future looking. We have patents data from around the world. We worked with IFI claims. They have 100 million patents in their data system. About 34 million have been integrated into the system so far. So there's a lot of work still to do. Clinical trials. We've been working with all the clinical trials, outlets which make data openly available. And so again, what we've tried to do is pull all these data together, but of course that's only the first problem. The second problem is then to actually enhance it and actually be able to do something interesting with it. So we try to create a modern technology stack. So there's very little human interaction in this. There is a layer of curation in it, manual curation, but almost everything is done algorithmically and using artificial intelligence. And what we do is we take the data from all the sources that we've talked about and we use AI technologies to try and do entity resolution within that set. That then gives us this kind of entity graph of things in how they're connected. So now in dimensions you can look at a publication and you can see the citations between publications, but you can also see the grants on which it relies. You can see the clinical trials which refer to it. You can see the patents which refer to it. And later this year you'll see the policy documents which refer to it, which I think is really exciting when it comes to social sciences. We also wanted to connect academics with content. So we tried to create a way where you could just click a single button in the system and go straight to the best copy, the version of record. So rather than having intermediary steps, there's one click to do that. We also have an API available which allows you to pull data out of the system. We wrote an entire domain-specific language so that you don't need to understand our data structure and you can automatically pull data out of the system using that approach. One of the things that we've done for free, there are two major things we've done for free. One is that there's a badge that you can download from the system. You can take the JavaScript advice that's from the website. You can embed that in your digital repository and you'll automatically get a nice little logo which gives you numbers of citations and some nice little metrics and goes away and gives you a full list of all of the citations. And the second one is that you can go to dimensions.ai right now and you can see the full publications and citations index for free. Anyone in the world can interact with that. Thank you.


Deja Rasha na teita, laka raka. Yaneza kwa wajushu that.iqu doka na m睼zi. Yaoneza, Shaddrako, kwa kwa ajutai. But bayanut za mtibama. So, kwa nda hii kwa di yutia. Mwa niwapki sewa katutu kwa gapia. Bida kwa. Bida, bida, bida. Iyawey. Si indiviju говорi sowa. Isnu kwea. Isu na isu na kwa. Isu ni kwa crei. Isu ni kwa fatao. Powerun iwapia. Jarret, yeahbohain mo. Hi, am Jarret watching kwa kichumu. Nisha zi mwu dijera, nisha zi dunda by valiant please. Join jo kifu na kuru, please play for me, Chris Moodpati agen. Jaridu dhi ambu agen, hain, nisha zi dunda by valiant. I think that's a repeat of something. I wouldn't be there from member Kassin, nisha zi Chris Moodpati.  Lakin I like the enthusiasm. Ita tafuto, ita chezwa. Our first guest goes by the name of Chris. He's an uprising gospel musician. Welcome to the East Circuit. Before we start, would you like to send a shout out to anyone? Shout out, na kwa Chris taraka, I easy fake aleo. Ahaha. Ewe ngnini kwa asi whato na ni watch. Nisha wu inspire in my songs. Napiya like my friends at home and my supporters. Na big어 sana. Napiya kwanza dashi qiwaiz kwa me numalisha aleo. Dashi qiwaiz. Dashi qiwaiz. Naka shop Naka shop And so, to link up So now you started singing at the age of five Yeah, practically Lijwa, ili upasi, upasi, ume throw up na around charts So you just automatically, you know Sunday school ni muhimun, laze mo you end up just, oh I can sing So na say ma talent zingile zi naka mingi jwe environment Yani place ume lilewa Is it something lulikwana poshiwa two words by the parents? It's something you just wanted to do Aii is suku poshiwa Lili kii nikitun wada penda sana Since I was a child So lilikwa daka like, mostly like my life I glorify God through my music, through dance So siko is kumewa Lilikwa nile kila siko tu yani Ni routine, ni routine tu yani It's our own motivation man, ni passion That's very interesting and I commend you for that Because as you know, our generation is one of a kind Even our old folks, they're like, ay, awa toto So how do you stay true to the faith And how do you stay motivated to do the right thing And what's it called? Christianity Not really Christianity There's a word I'm looking for When you're doing something for the faith To stay true to the ministry By dancing and singing How do you stay true to that When there's all these other temptations I think ni kujiwa papasiyako Kijwa papasiyako ni gani Ita kwa ngumu Beide kuna weneza ingi Kavile gadi enu usema He's my mentor So kutkio akne gadi enngil Na usema Beide kawome kama for the wrong purpose Io tu yo purpose to ita kutu The very same purpose So kama mibilu kumekami ado Let's kudu ita isya Wene na hepe yo na chomoga So wakati mianza ku-understand Kwanza na fanya gospel Not as an industry But as a ministry Ina kwa impactful Kwa life here kuna atu And they start seeing the fruits of it And they say in the business for longer Like we grew up watching all these Gospel musicians and even secular musicians We went to gospel and gospel We were now somewhere In bitu Kuna wakatu mahali They're like I never said I'm this I never said I'm that But in terms of content creation Kenyan gospel music Kuna wile it's mostly dance music I think you get what I mean It's not really ministry focused So what do you have to say to that? I think every country Music is blessed It's graced in a certain way Of doing music South Africans they're still Their culture Uta patangu maya yoni beats too Kutaka mwanzu police na sema tu Maichuku ya Maichuku ya Kiyotu ndo tu na sema kuyo song Una pata And I think since nzakale Kwa tu lukuna jua Kenyans are like these people who are hyped Sisi na Nigeria kuna wene atu na Una pata squeeze na hype song Zitu zi na ndakufana na nazao I think we're also growing Because Kiki kumpiapia na atu kama sinach Kuna zile witu like Kuna zile secret rooms ame ingi yao na Praia Sisi sema atu Atu kodifrensa na Nia atu kuna Kresitofa uti Yakufanya the style of music So maybe una pata sinach So that's where God ame ingresia So kipata uku kina Gadi eno na hoa Gimana guwanzu Witu wile zisa utu saputi ini Like as long as una bring the right content It's about gospel, it's about Christ Siu nikama kuna uba atutapatana What's about that other situation Of where people don't have a stand They're doing both Nikama this guy just sang This latest hit song in Kenya To atu miyadarati It's sung gospel the other day So do you feel like it's essential And important for an artist If you're a gospel musician To take a stand and say Minim to a gospel Siu atu niku mahali What do you think? I think maybe I didn't have a more address Due to Namju and Steve who seem to boil I make too clear I make too clear Ako api Ako inspirations Ako api vijana Ako inspirations Laka ni atu end of it all This world it's a demand to stand Ako una stand Aki tufani ni atiadi watu Siu sugo atu kuiduni Ako ataka kuiduni Ako api Ako ile pande Ako kuna kuka kua first Nasi kikunglu kuna di Uli pol If you fall Siu on your toy Call it take for a long time Maybe it's game business Aki vili nama ju e liana Naak around Iokung luya kosushu media所 nani aki ni more clout than anything else But that's difficult though That's another question I would like to ask you You're an uprising artist You've seen the extent The major things people do Just to stay relevant Like Willy Pol How do you say you're relevant without jeopardizing your faith and your ministry? Onana kuna line ni anyofu wa iku cross? Ya, like unafa utupu set boundaries ako. Like one of the people wa ataka unge kuwa live today, unge kuwa na celebrate ni kabere re. These are people who are strict in the gospel. Like niva sayo wa luku wa high fanyu because like ni wa nataka glorify wa na ona. So that's why they say ma, oku wa tuu na umekam na the wrong motive juu kichi kiburada eitu. Badu na mombeya. Na vila lingya na sito liya. Mi wa duju liza. Kuna wene ni willipole na ndangi kuizosong zaki na scroll na naichi ki. But they will leave it. Po lipa na luku wa fiti like, what has happened? Onana. So I think ni ku stick close na God. Stick close na God. Wacha God ako tu rafiki ya ako. Siko ni relationship liya kuna na God after wanu kama salio na ndakutu angoma. Like kuwacha wiki kwa yu okulu. Especially since now, obviously willipole by there. Come on, how much they say it. Zika ume umkama wu zia umka. But you know, there's so many people who are looking at you, especially in the gospel music industry. So magnifying glass ni bigger, right? If people need to take a stand, not aside now, let's focus on you as a musician. In 2017, uliya zaku tu angoma flani. Was it really gospel ama ilikwa inspirational? How can it classify it? As long as you're sending the right message or even unifying people, God nai say ma God ni love. No na. So as long as una dati to kwa life ya ako, kwa musiki ya ako, na umatambua Christ. Nadia kwa Christ nai say ma, wiki yawata say ma, oh li kwa nakudyua. Nkini Christ tai say ma, As long as me receive Christ kwa life ya ako, and then you're doing it as good. So I wrote that song because in ikwa nachiki kumanzi so tensions are kabila, so I wrote a song in itwa we are one. Kenyans we are one. In any personal situation, wu li pili li kwa affect to that extent that you had to put pen to paper on the keo imbo, we are one. I was just reflecting from what had tried to happen in 2013. And I thought maybe this time nai za kwa kwa Christ nai na. No na. So ni li kwa kwa like better, una kwa kwa umbele. No, prevention is better than. Kwa so ni kwa nakuanzi nini kwa song that maybe nai za inspire hatu. If maybe imu say alwa kwa na fukiria kuna kitua nai za fahanya, inam cool down. Because I always believe this power in music. Music just unifies people. It just unifies people. Just like the song says we are one. We are one. Nice, I like that. And I think DJ is, I don't know if I should, you know, new or point fingers. Because we need most of these songs to be played in the clubs. How we feel? Because we were so hard by there. I said for that song, we almost struggled like for like almost like six months to nai na kwa kwa copyrights nini. And we are almost giving up and can't be a producer anywhere to give up. Because he is a fairy to me anza. It's like to me shu kwa matata. So I really encouraged even my producer and he was the fan of me be wherever he is watching. He is the owner of our focus. Produce here the first songs and he meant us ana kwa miziki. Kaku anisha what to do, what not to do. What not to do. Nice, I wish we had some more time to onge about the music industry, especially the gospel music industry and your take on it. But unfortunately, I tell you me nanda kwa isha. But unfortunately, I tell you me nanda kwa isha. So let's talk about the 2019 song, the new one. You released it around July? July. I like the vibe of it. You want trying to be anyone else. You want creating a dance song.  So let's talk about it for a minute. Um, aneze se likin li aniki yo song wakatilis kia my friend, fellow friend alukwa nishi kasa. So alikomit suicide. And it really pained us because nim say tulisoma nae, tukagro nae, like alik provide you the best facilities, the best education and you are like, guy man, uli fanya ni ni. Like uli decide aji tu yani, kwenatukchuku appeals, kujiniwa nga, you know. And it became so painful. Up to date baduna kumuka nga, yo story am like, hey God, I wish kuna wene zah reversing ni time, no advice. No, no. So I wrote that song out of like a dedication also to him and dedication to all the Kenyans because at that time, I think yo time period, yo period ya April me, kulukwa na tu visanga tunas ke manjana. Kulukwa na tu many issues na ya vizana ya. That's very true. So I wrote that song, not to train like maybe to to be different because kwan me pangai, yo mua kabe, there was to do some like same hype, hype gospel. But ni kasa, mua chatu kwanza ni toe this. So you get that off the chest. Yeah, then the next maybe you shall have something to vibe, to hype. Is that what's coming next for you? Yeah, yeah.  But you have to be okay, too. You need to raise a good friend. He's not really excited about it. Anyway, I am a dance leader at the church. It's okay. So I have to lead kusini to authentic teens. So to kwan authentic dancers. Maybe I'll be invited to invite them in a while. That's exactly what I want to do next time when you come and we discuss the gospel music industry with a new track, I want you to come with the authentic dancers. We see. We see. We see. We see. We see. We see. We see. We see. We see. We see. We see. We see. So were, they will do that next time when you come through. Sante Sannah for coming 2 where can someone find you in social media? Uh in social media platform Zanguzote in Chris Judah Facebook, Instagram. Yeah anywhere. Twitter, since Judah. Safika Bisene so next, Chrisijoe's with his latest song.


Okay, so in the last two videos video number one we installed our pixel. Okay, we installed our pixel we put it all in all across all pages and and and now now now our pixel is tracking this most important data. I didn't know when I thought the recording was on I didn't know you turned it out that that's video number one video number two is we set up custom audiences around everyone who's landing on all these specific pages okay. Now, in this video what we're going to do is we're going to simply create a custom conversion, which is the most important. And again, let me explain what a custom conversion is. This is the most important without a custom conversion you're not capturing leads without running conversion ads the right way, you're not capturing leads. And so that's why this video can apply to a lot of different businesses, because most businesses that are running Facebook ads, you're nine out of 10 of them are doing it for one reason. That's to capture a lead, you're either capturing a lead, or you're making a cell. So if you're selling a product online, then you're running Facebook ads conversion Facebook ads to get people to buy your product. If you're not selling a physical product and you're selling coaching or consulting or any other type of service. And you're, you're, let's say you're giving away an ebook or you're you're getting people to register to watch your webinar, or whatever maybe that's a lead, that's lead capture. So you're either looking to capture lead or make a cell bottom line. And to do that successfully on Facebook through Facebook advertising is you have to set up a conversion event. And so in this case what we're going to do is we're going to tell Facebook what our conversion event is we're going to set up a custom conversion. So here's here's what I mean by it. So as I scroll through the news feed and I'm just seeing what everyone's up to. And then all of a sudden I come across a sponsored ad here goes Russell Brunson. There goes the text. There goes the video. Here comes to learn more button. Here's a custom conversion. Now, in his case what he's doing is he's actually selling a book. Is this regarding his, his lead, his book. Okay, so here. Yeah, so this is just this is a perfect example. Okay, so as I come to his page. And all the ad, I clicked on learn more. I came to his landing page. Okay. I come to the landing page, I click on the button, and it brings me here to this order page. When I fill out this page, name, email, phone number, full name and I go through the full completion, and I click on, send me my swipe file now. And that button, it's going to take me to an order confirmation, just like in your case. So when I come to, when I come to your product, when I come to your product, or when I come to your landing page I should say when I come to your landing page. I have to put in my name and email to get to this page. Right. This is a thank you for registering. This right here is the most important conversion. Now your purchase conversion. This is the purchase page. This is the add to cart page. These conversions are important as well but what we're going to do is we're going to simply focus and keep it super simple and focus on this one. Thank you page. This is the conversion. So a person has to go, they have to see the ad. They have to click on learn more. They have to go to your landing page. They have to enter their information to ever get to this page. Does that make sense. Yes, yes. So, so, yes, they get this page. Let me pull up your landing page just to give us a real clear example. So let's get rid of the Russell one because that's purchasing and that's fine if I click on that red button. I go to the thank you for purchasing page. That's the custom conversion. So in your case I come to your landing page. I have to register. I have to put my name and email in order to get to this page. This page is the custom conversion. So what most people try to do is they say okay I'm going to run a Facebook ad because I want to get people to my landing page. Okay, that's fine. And that's what Facebook is going to do. Facebook will run the ad to get you people here. But I don't want people just to come here. I want people to come here. I need to be very specific about that. I need to tell Facebook where here is your goal is to get them to click learn more and come to the landing page. But your ultimate goal, your ultimate goal is to get people here. Facebook wants to know your ultimate goal. They don't care about your goal. This is your goal to get them here. Your goal is to get them to click learn more and come here. That's your goal. They don't care about your goal. They want to know about what your ultimate goal is. Our ultimate goal Facebook is to get them here. And in order for people to get here, they have to smash the orange button. They have to enter their information in order to get here. So as we set this up as we set here up, this is the thank you page as we set this up as a custom conversion. We we're going to start running Facebook ads and Facebook is going to start finding this people that are most likely to get here.  So so so we're not telling Facebook we want to get people here we're telling Facebook people we need to get people here. And so here's what we're going to do we're going to take here we're going to double click. We need the link we don't need the HTTPS we only need the URL we're going to copy that. This is the thank you page. We're going to come over here to Facebook we're going to click make sure we're in the right account we're going to click on the dots up here. We're going to go to events manager. This is how you set up a Facebook custom conversion. And again this is for anyone and everyone who is looking to capture leads or make cells.  And it's just a custom conversion that we're going to set up ourselves so we can name it ourselves and name it what we want to name it. So now here's what we're going to do. We come over here and right over here from our previous video this is where we get our pixel, but we're not going to get our pixel here, we're going to simply hover over the blue triangle, and we're going to custom conversions. So here, what we're going to do is we're going to simply create, we're going to hit this blue button, and we're going to create a custom conversion. So again, I copied the URL on the thank you page. I brought it over here. So I'm going to name the conversion this is storytelling, storytelling leads, anyone who lands on this thank you page is a lead. Storytime storytelling leads, make sure that that's my pixel. I'm going to go all URL traffic just leave it there. And we're going to simply select our own category. I'm going to hit the drop down. I'm going to come down so there's all these data points so I can create a custom audience around add to cart which we are going to set one up. We're going to set up a customer in fact yeah we'll do we'll do, we'll do, we'll do, I'm going to set up all three of them we're going to set up all three of them right now might as well. What we're going to do right now is but there's all these different data points we're going to focus on this one this is lead let's just do the lead real quick that's lead. So now I'm going to simply take what I pasted, and I'm going to copy it right there. Okay, storytelling leads, we're going to click create and here's what super super important here's what you absolutely have to do. I've created it. Now up here, it shows inactive. What I have to do is I have to come to the page. Over here in real time and refresh it. So if I come to the page and refresh the page, then Facebook now rereads it. And now if I click on the Facebook pixel helper. Now look what it says leads. That's why when I opted into the Ted McGrath one, right. I clicked on it and it said lead. Yeah, we customized ours, and we're naming ours storytelling leads, because we want to be specific and we want to know what the hell our stuff is so we we customize it. He just left it as the default lead, but I want to I want to I want to customize this because we're going to have different projects and we want to know exactly, you know this conversion so storytelling leads I refreshed it here.  And this inactive should go active. Let's refresh it here. Active. Oh, it is. That is the thank you page. Now what we also want to do is create another custom conversion. Okay, we're going to create another custom conversion around the cells page. Okay, people that land here, people that land here now again we already set it up as a custom audience. But what we also want to do is we want to set it up as a custom conversion, because as we go run future conversion ads, we can split test. And we can we can tell Facebook hey, we need people to get to the thank you page, or we could tell Facebook we're looking for people that are likely to get to the cells page. It's very specific and then we're going to create another custom conversion around the purchase confirmation page. So these are data points these are these are ways to tell Facebook hey man I'm looking to get people here. Find me people that are likely to buy find me people that are likely to land here. So ultimately, these are the three, the thank you page, the, the add to cart, the cells page which is the cells page, and then the purchase confirmation page. So we did the thank you page already. Now let's do, let's do the cells page, this is going to be the cells page. So I copy this, and I come over here, and we're going to name this conversion story, telling cells page. Story, storytelling cells page cells page, which is actually called add to cart atc. So now here's what I'm going to do. I click on this right here select your own category, I hit the dropdown, and we'll see it right here. Add to cart. So again, it's a custom audience we already set up a custom audience that was on on on the previous video. Those videos will all be in the description if you didn't catch any of the videos, watch all three of these videos this is the third video of our series right here video number one was the pixel video number two was the custom audiences. And then now today video number three is the custom conversions now we set up a custom audience around everyone who lands here on the cells page. But what we're doing now is we're creating a custom conversion around the cells page and all that means again is when we go and run conversion ads. We're going to be able to tell Facebook. These are the type of people were looking for that's very different than the custom audience, the custom audience allows me to retarget the people who have already landed here. But I'm running the conversions ad for future people. And now I'm going to tell Facebook, I am looking for specific people I am looking for people that are likely to land on this page. So it's a custom conversion it's an ad to cart storytelling cells page atc. So now all I'm going to do them a copy. And I'm going to come down here, paste, and I'm going to create, and I can add a value but but I don't we won't add a value right now. In fact, you know what let me add the value let me add the value because you already know, you already know the price of it. So let's add value and we're going to name this one for 497 for 497. So this is right here, we already got the description. So we're going to hit save changes. And now you'll see the value down here 497. Okay, so, so again, as people start to purchase, then you'll start to see these numbers in your dashboard how many how much money you made. Like this is where we now we're going to be able to see all that through Cartra, because everything is being processed through Cartra but at the same time we can see it through our Facebook ads manager, based on the analytics and looking at the analytics because we're filling in all the blanks. So, so that right there is the add to cart. So now again, it's inactive, I got to go back to the page, I got to refresh it. And then if I hit the Facebook pixel up here at the top. We're now going to see now. What's that. No, I said it's green now. It shows what you were telling me it's green now, and it shows up here. It's gray. It's gray right now. Right here. Oh, I was talking about something else then. So if I refresh this page so I got to refresh the actual sales page and then I got to come over here to Facebook and refresh this page. So when I refresh it, then it turns green, then it turns active. And then we add to cart page. Okay, so now the last one we're going to create is we're going to create a custom conversion around the purchase confirmation. And again, something right here. You see how I cross that with black I couldn't figure out how to use a red to cross that 997. Just just go into the colors and change it to red. That's it. It's just changing the color inside the highlight it and then you'll have the ability to change the color. Yeah, okay. Yeah, so, so now. And the way to look at a custom conversion the way to look at a custom conversion, a custom conversion is your end goal, the end destination. So as I step into Christie's world, I step into her world from the landing page. Where is she ultimately trying to take me? Where's that page? That page is either the thank you for registering that page is either the sales page or that page is also the purchase confirmation, the end goal, the destination. That's a custom conversion. Where are you trying to take me? Let's let's let's cut to the chase and show me that page right now. This is a custom conversion. Facebook just wants to know, Hey man, cut to the chase. What's the end goal? What page are you ultimately trying to get them to land on? I'm trying to get someone to land on this because if they land on this, that means they bought. Now, again, you have to edit this because this is not, you know, this is this is what we cloned from the previous page but but I'm just giving you the example. So this is the end goal. Anyone who lands on this page purchased. This is the purchase confirmation.  We created a custom audience, everyone who lands here is a core student. They purchased that's a custom audience. But what we're doing now is we're creating a custom conversion. So when we go and run the ad, we're going to be very specific and say, Hey, Facebook, go and find me people go and find me new people go and find me not in my custom audience yet. Go and find me people who are likely to land on this page. Go find me the buyers. We're going to tell that to Facebook on day one, because we told them about the link, and we set up a custom conversion. So, again, we copy everything other than the HTTPS we come over here. We're going to create conversion. We're going to name this one storytelling storytelling course students purchased. And again, you can always rename that. So there's that, but you can leave it like this as well so that's perfectly fine and then we come down here select your own category, hit the drop down. And now we're going to name this one. This is purchase. This is the conversion event. This is what we're trying to tell Facebook from day one, when we go and run that ad, we are looking for people like this we're looking for people to get to this page. We paste in the link. We hit create. We click on done. It's inactive we go back to the page we refresh it. Anyone who lands on this page is in a custom audience, but also everyone who lands on this page is a custom conversion. And there it is there we come back over here we refresh this page. And now this inactive should go active. So again, this is Facebook custom conversions. This is for anyone trying to capture leads or make cells online through Facebook advertising. You want to set up these custom conversions. First. So, so look, now that we have these up and I'll say this party and closing. Now that we have these three active. Look, here's what we can do now. As I come over here, back to my back to my dashboard. Here's what's amazing. Here's what we're going to be able to customize now. Now that we have those customized, I'm going to come over here and I'm going to make sure we're in the right ads manager right here Christie's ad manager. We're going to click on columns performance. And right here you see the column campaign name delivery, bid strategy, budget results, reach. If you take this all the way impressions cost per result. There's a lot of data points up here that we don't need. If you click on assets. You got ads that name delivery, bid strategy, budget results, reach impressions cost per result. All this stuff. A lot of the stuff links link clicks three second video plays like a lot of that we don't need. Same thing with ads. You're going to have that column all across the board. What we want to do is we want to customize it. We want to customize it. So when we come in here and look at the dashboard, we can only look at the most relevant data. And that's it. I don't need to look at all this other crap, like I just need to know my bottom line numbers and I'm going to show you what those are.  And now what I'm going to do because I set up my custom conversions it was only because of that. Because I set up my custom conversion. In fact, I can still change this and see what I want to see. But but I really am doing this because of my custom conversions. So now that I have my custom conversions. Here's what I'm going to do. All this stuff over here to the right. I'm going to delete a lot of them. I'm going to X out a lot of them. So bid strategy, last significant edit don't need results. I'm going to have my own custom conversion to read the results. So I don't need that reach. I don't need that impressions cost per result quality ranking. I will leave that engagement will get rid of that conversion rate ranking amount spent and schedule link clicks. I don't care three second video views. I don't care video percentage watched. I don't I don't care to see that on the dashboard video average play time, whatever we don't really need that. So we'll leave these ones delivery ad set name. bid strategy will leave that budget quality ranking amount spent ends and schedule. Okay, so now here's what we're going to do. We're going to come over here to the left to our custom conversions. And these are the ones that we set up. We set up the storytelling core students purchased the cells page at to cart the storytelling leads and and this actually we didn't do the schedule appointments. That was that was what you had before, but it's for this specific campaign. It was these three. So here's what I'm going to do. I'm going to check the total, the total, the total, and then I want to check the cost, the cost, the cost. So now I have all those added to the right. I checked the box and they all get added over here.  I'm going to drag them. I'm going to drag them to the top, take that one. Let's take. Let's take that one purchased storytelling course. Actually, I don't know why it's twice, but we'll just delete one of them. storytelling. Okay, so that's the purchased. Okay, so storytelling core students purchased storytelling page core students per I don't know why it's twice, but let's see. It's right. We'll just put it at the top. Okay, so, so we got cost per storytelling lead. We got cost per storytelling students. How much is it cost us to get someone to buy. How much is it going to cost us to get someone to opt in to be a lead. And then how much is it costing us to get people to the sales page. Everything is a data point. Everything is a data point. How much did it cost me to get the lead. How much did it cost me to get people to see my sales page. How much did it cost me to get people to purchase. These are our data points. So now over here the bottom left save as preset. Story telling campaign. So now, now storytelling campaign I click apply. And now whenever I'm in my dashboard, and I want to look at this specific campaign, I'll hit this drop down, and I'll go to storytelling campaign. And now look at the way everything looks. Now I can see right here. The cost per storytelling lead, the cost per sales page lead, the cost per student. So now I'm able to really look at this. These are the only data points I need to know how many leads came in. How much was spent. How much did it cost me to get someone to buy 497. I can start looking at these data points right here as you start to run more ads. That's powerful right there. Yes. So that right there was Facebook custom conversions again don't worry about remembering any of this I haven't recorded I'll send you the recording watch it 50 million times if needed. But that's custom conversions and customizing your columns. Did you send me the recording for you. I will I will I will so any questions on this regard. No, I don't have any question here. Okay, so. Yeah.


So, I've been asked, why does all property have to be private? And there's something deeply flawed about the question, because all there is is private. All there is at the end of the day are individuals. So all property is owned by somebody. Now, it could be a group of somebodies in a sense of a corporate entity, some kind of a partnership, you know, some conglomeration of individuals that are legally bound. But there's no such thing as, so that's private. The alternative to private property is that nobody owns it. It's either somebody owns it or nobody owns it. Now, I know that you're thinking of why can it be public property, but there is nobody that's the public. There is no entity that is the public. The public is just a conglomeration of individuals. And those individuals have particular rights, and one of those rights is a right to property.  It's in individuals that own stuff. So public property today is really owned by nobody. There's, you know, the, or you could say the government owns it, but who is the government? And how did, what does that mean that it's government owned? And this is why there's so much confusion about how do you deal with so-called public property? How do you decide? Let's take public schools. How do you decide what should be taught in the schools? Do we vote on what the truth is? Do we, you know, do we vote on what math we should teach? Do we, I mean, do you teach creationism or evolution? Well, how would you decide in a private school? Well, the teachers would decide and then the parents would decide whether to send their kids there or not. It would be private. The private owner would make a decision. But in a public school, how do you decide? What is the criteria? There is no criteria, there's no criteria. If you have a piece of land, should we turn it into a natural reserve? Should we drill for oil? Should we use it to dump all our garbage? Or should we, you know, sell it? How do you, how do you make a decision? Vote? Why? Why should the majority force the minority to use what supposedly, at the end of the day, it doesn't belong to anybody. So there is no standard by which you decide how to use it. Public property is not owned by anybody and that's why it's usually in such bad shape. Public institutions in bad shape. Public education is a disaster. Public anything is a disaster. For that reason nobody owns it. So the only alternative is private ownership. Individuals, because only individuals exist and, you know, individuals are the ones who create stuff and private ownership at the end of the day is a product of being productive, of creating wealth. If you as an individual create wealth, it's yours. It's private that public doesn't create wealth. Public doesn't build anything so it can't own anything.


My sense is that people react much more quickly today when there are levels of abuse and patterns of violations that are simply unacceptable. We can think of what happened after Abu Ghraib. We can think about what's happening currently in Syria. I'm convinced that the Geneva Conventions have stood the test of time. Now clearly, when you look at what's happening daily in Syria, Afghanistan, Congo and elsewhere, where women, children and civilians are caught up in atrocious conditions and huge suffering, it is a legitimate question to raise. And there was a vibrant debate after September 11 about whether or not the Geneva Conventions were still relevant. But they were negotiated just after the single largest and worst calamity that mankind had inflicted on itself, which was World War II. And so it has to be a body of law that is protected, enriched and further strengthened to remain vibrant on a daily basis. Do you think the world is becoming more or less tolerant of violations of international humanitarian law? My sense is that people react much more quickly today when there are levels of abuse and patterns of violations that are simply unacceptable. We can think of what happened after Abu Ghraib. We can think about what's happening currently in Syria. It may not change the situation, but I think people are highly sensitive to these types of situations and these types of violations. People are highly sensitive, but some states, the United States comes to mind, would say that in certain circumstances their own security takes precedence. Often when we talk about universality we talk about we have rules and they apply to others. But the test is whether we apply them to ourselves when our own security is at risk. And that was after September 11 a debate we had extensively with the U.S. but also frankly with many other nations about whether really it is credible to put one's international legal obligations on the back burner at the moment where one's own security is at risk or whether it wasn't true that one can balance one's own legitimate security concerns with respect for one's international legal obligations. And this is a debate that will continue. The changing nature of warfare, most conflicts are now within states rather than between states, many fragmented groups. How do you actually reach all of those fragmented groups and make sure that they do respect these rules of war? Fragmentation of our groups means concretely that when ICRC or other organizations are dealing with humanitarian consequences say in Congo we deal with 45 different factions. The names change regularly, the affiliations, the motivations and the reasons for them to be fighting change and vary. To be able to reach them and sit down, as the ICRC does in dialogue with all parties to try and influence a change of behavior is a painstaking, sometimes dangerous and highly challenging effort but it needs to be supported by the wider international community. These non-state armed groups, they're not signatory to the IHL treaties. In some cases they actually use terror against civilians as their modus operandi. So how can you actually expect them to respect the laws? The first thing is that IHL does impose obligations on any group in an armed conflict. Now it is true that some obviously have not signed and do use deliberate tactics that target civilians. In this case the only thing that you can do is to sit down in face-to-face dialogue with them and try to identify the issue that will resonate with them. Some may be that they understand also for them that respecting the wounded which can concern them is an issue that is of importance to them, their group, their families. The other one is that the idea that humanitarian organizations should have access to a region which they are under control is important for the wider communities not just for the ones on the other side of the front line. And so you build a patient dialogue but it is to understand the perspective also of the other as challenging as that may sound in our work and to then build links in that way because ultimately it's only by reaching out that you have the potential to influence. So it's constant patience and it's small steps. It's in particular being clear about the fact that we don't take no as an answer easily and we keep coming back and it's this sort of stubbornness of the organization because it's our only weapon if you want to use that expression is to engage in dialogue in principle not to judge the other one which is another challenging issue in human terms because of course you sit with people that are not easy to approach and that are not easy to think about, to identify with certainly at times but it is if I judge the person I break the bridge that may be the one that helps me reach prisoners or make a difference for civilians somewhere.


Have you ever had an a-ha moment? That feeling when everything just seems to make sense. Scientists have them all the time. Hi, I'm Jim Green, NASA's Chief Scientist, and I have discovered many new things in my career. And let me tell you, there's nothing quite like that feeling when you discover something important that no one in the world knows. What if I told you that through NASA's Citizen Science program, you too can experience that same feeling? Are you interested? Citizen scientists working with NASA have made many significant discoveries, some of them right from their own home. For instance, 54,000 Circumstallar disks have been found by citizen scientists. What are they? These are debris fields around stars in our galaxy where planets are being formed for the very first time. What about the citizen scientists that have discovered 18,000 mosquito breeding sites in NASA Earth science images? Breeding sites like these are important to first flying, since mosquitoes carry all sorts of diseases. So there are many other discoveries going on in NASA's Citizen Science projects. And you can get involved.  I am sure some of you might be saying, well, I don't have a fancy degree, or I can't discover new planets beyond our solar system, and you'd be wrong. You don't have to have a special degree or job title. In fact, you don't even need to have experience. If you're curious about our universe and about our planet Earth, you can get involved with real NASA projects and work alongside real scientists right now. So what are you waiting for? Come on and join us. To get started, go to science.nasa.gov slash citizen science. See you there.