You can now follow me on all my social media platforms to find out who my latest guest will be and don't forget to click the subscribe button and the notifications button so you're notified for when my next podcast goes live.      Someone like Tottenham, let's say, would take 5,000 away. There'd be 400 up for a row and the other 4,600 would want to watch the football. With Millwall, there'd be 5,000 away. There'd be 400 up for watching the football. 4,600 ready to have a row if they needed it.  And we had two options.    If you've tried everything, everything that possible in order to try and infiltrate this gang or this cell or whoever and your only way of getting in after everything you've tried is via the sister, let's say, of one of your targets and you know that that's gonna get you in. Is there a justification in order for you to do that if you've tried every other option? I'd say, yeah.  And we're on. Today's guest, we've got James Bannon. Hi Mike, good to meet you. How are you, James and Bill? I'm good, I'm good. Very fascinating story. Thank you. Undercover cop went, get involved in one of the biggest firms in the UK football hooligan, undercover football hooligan, basically for over two years, it wasn't just a short job, it was very long to be fair before we get into that first and foremost. How are you? Yeah, I'm good. Again, thanks for taking the time to be here today and obviously come on the show. It's a pleasure, Mike. People love these sort of stories. I always go back to the start of my guests. Where do you grew up? How it all began? Grew up south London. Dad was a policeman. Mum was a home help, lived on in a state.  Didn't really do school, hated it. And yeah, I had to make a decision, made a choice when I was 16, I joined the police cadets, which was for me at that time was the best thing I did. And I had two and a half years of raps around some really nice guys and girls, to be fair. And then came out when I was 18 and a half, went to Hendon, 19, got posted to Greenwich, went on the beat, wasn't on it very long at all. I think I was in uniform before I went into plain clothes after about six, eight weeks on the area car. I did bits and pieces in uniform, but most of the time I was working as plain clothes observer on the car and which is basically you're in the back and there's a bit of burglary or there'd be an incident and you'd get dropped off with a PR and a radio and just see if you could see anyone. And being young, these people wouldn't look at you and think ordinarily, instantly, that you were a cop because you looked even 19. So yeah, I did that for a bit and then got on the crime squad after 18 months, got special dispensation to do that, started on the crime squad and then came out of probation and then pretty much got the nod to go from an interview at the Scotland Yard to go and work in a covert environment. Was it a decision for your dad as well or was that something you'd always wanted to be? No, I suppose all of us, not maybe not all of us, but it's always quite fractious with boys and dads, so it wasn't the best relationship at that time and I went in really basically because he didn't think I was going to amount to anything. Why? Because I was, I got expelled from schools, I had a really tight set of mates that we hung around with together and we played hard really and he struggled with that a little bit and I was quite, not unruly, but I was my own person, I knew what I wanted, which was I didn't want to go to school, I just wanted to make money. So he said I wouldn't amount to anything and I thought it would be quite a good idea to do what he did and just say, well look, can't be that hard because I'll even have someone like me, he won't amount to anything. What was your first day in the bit league? First day. So I had a really, really, really great mentor. I was very, very lucky. So I had a guy called an Ablaug Sergeant who took me under his wing. So my first day he's, he's a puppy walker, which means that they come out with you. He wasn't that sort of policeman. So he was an ex detective chief inspector that had been busted to sergeant. So he came out of the clubs in London and came back down and was working in Greenwich as a uniform sergeant then. And his words of advice, I'm going to give you three words of advice. So I went right okay.   So I went out. I was out, it was two o'clock, shift, so I was working two to 10. I went out at two o'clock. I'd been in the collater's office, which is back then, which is what pictures of all the people that were wanted and stuff, recognise the guy, Big Rastafarian. But that guy looks very similar to the photograph of the guy that's wanted in Leicester for something. And so I approached him and he ran off. So I chased him. So I ended up having a scrapper with him. He was a much bigger man than me. So I just hung on to him. Screaming, urgent assistance. He needs to come and help me because this is a big guy and he's much bigger than me. And I was basically hanging on to this guy. We got him back to the station. I've got my tunics all ripped.  My tie's gone.   So I'm back in the station at half two. Anyway, transpired that the guy was wanted for rape and of a young girl in Leicester at the back of the Kentucky Fried Chicken Shop. It's amazing what you remember, really.  So that was my first day. Within 10 minutes I'd made an arrest of a geezer that had been wanted for a rape. So a good day for all, really, apart from the guy I got nicked. I'm having a great day for him. What was that feeling like for you? It was the first person I'd arrested and I'd been out 10 minutes. So it was a great feeling.  He had done a nasty horrendous thing. And I'd managed to catch him. And he was going to go back and he was going to be held accountable for what he'd done. How's that feeling then, but to go through that straight away, the first 10 minutes in the job, did it make you question the job? It was the right decision? Yeah, totally.  No, totally. What have I signed up for? Totally, I was 19 years old.  It was massive. And for me, it was because it set me up. And I got a nickname. My nickname was Golden Bollocks. Because I just, everything I touched, everyone I stopped was either wanted or... And the reason for that is I stopped loads of people in my short uniform period of time. I did loads and loads of stops. And loads and loads and I did all my research and looked at all the collators, obviously, who were wanted, found out who had warrants against and all that sort of stuff, stuff that you should do. And I wasn't lucky.  And it paid off. Because ultimately in the end, I started to manage to, started to arrest a lot of people. Because if you stop a lot of cars, the likelihood is that one of them is going to be doing something they shouldn't. Do you think it was easier to catch the bad guys because you're from the streets, as a young kid, to notice them more? I think so.  So they don't have eye contact. So, yeah, it helped that I, you know, I'd been picked up from school when I was 15 in a car that didn't belong to anyone. It's just because that's back then, that's what you did, you know, we shoplifted. We did all that stuff that, you know, maybe not everybody did, but back in those days, it was part and parcel of in South London and growing up. Yeah. How was that coming off the beat straight? I mean, how long should you've won the beat to be going clean? Two years. And how long did you do it on? On and off, I was in uniform for about 12 months. But even those 12 months, so within six weeks I was on the area car as an observer, which is the prime. It's apart from driving the area car, which is the big car with all the flashing lights, which is the hypersuit vehicle. It doesn't really get much better than that. And because of my mentor saw something in me, I got that. And I was making big arrests and doing all that stuff and doing all the observations on all the drug houses and then being the one to go and do the drug buys, you know, before I was 20 years old. What was the scariest moment on the beat for you? The scariest moment, which wasn't the scary moment at the time, is I remember we went to a house to arrest somebody who had committed an arm robbery. And I went round the back and jumped off the wall. It would only be me, wouldn't it? It jumped off the wall. And as I jumped, the ground all moved beneath me. And I looked down and there was a plastic bag and there's things sticking up at my bollocks. So I looked down and went, a bit curious as to what that is. I bent down and opened the bag and there was a son-off shotgun. So the guy got arrested and it was the gun that he'd used in the robbery. And then about six weeks later it came back from the lab that he had a... it was loaded and he had a hair trigger. So the likelihood and the chances of me jumping on that and it not going off for really... well, of it going off for really high. That's probably in realisation the scariest bit is I was going to lose my bollocks. No more golden bollocks? No more golden bollocks, no. So that was probably... but I mean, it's... it's elements of fear, you know? It's like, that's why stopping cars, searching people, they all contain an element of risk. Particularly if you do it a lot. So... So we see the plain clothes down here, is that CAD? Yeah. So you would only what, 1920? So I was... I wasn't a CID officer. So I was a crime squad officer which are uniform officers that work in plain clothes. And the idea is a stepping stone. So you go from crime squad and then you go to the... you join the department, so you join the CID. Yeah. So my natural process would have been crime squad another... maybe another squad like three area or four area drug squad as it was at the time. And then you would then go be... be selected for CID and then you would sit a bold, you would do that bold and then you would go to Hendon for more training. Yeah. And then come out as a detective constable. So at 21 you've went undercover football hooligan for one of the biggest firms in the UK. Yeah. My wo... Why so young, did you get that call? Because what you were doing previously I was like... Yeah, a tactic to send someone young in. No, I don't think so. I think, you know, there's a bit of a myth in relation to an... in relation to undercover work. Is this not age-specific? Is you can either do it or you can't. Whether you're... you know, you don't suddenly get to 30 and it's like, I can't tell you what, he'd be good at undercover. And I think my mentor, I sat with him and I asked him and said, you know, what do you think? And he went, yeah, I think you should do it. So I think you'd be good at it. And it was... It's a fantastic opportunity. I mean, it's the pinnacle of really, as a police officer, certainly for me, of working in an environment where you're trying to pretend to be someone that you're not. And you've got the option to be able to arrest nearly some really nasty, horrible people and put them inside. So did you know much about football before you got involved? Yeah, I knew a bit. I knew a bit. I'd been when I was a kid. I'd done Arsenal for three seasons because my next-door neighbour, one of my best mates, Dad, was a steward at Arsenal. So from the age of 10 to just nearly 13, 12, so nine to 12, we used to go every Saturday to the home games and get in for nothing. So he used to be the steward. So we'd just bring us in through the turnstiles. So we'd go and watch. Which was great. It was sort of Liam Brady times, Frank Stout, all that lot. It was amazing football. So we'd go to, yeah, to Highbury, at the Old Highbury and watch that. And then I got to 12 and I got a Saturday job. So I stopped going because I wanted to earn money. What was the plans for being an undercover hooligan? Was there a tactic to do that?    We had no, I'll tell you what we had. We had, I had a, which we made ourselves. I had a business card. The company I did was Spectrum Decorating and we had an accommodation address in Croydon. And we had a pager number because mobiles were around in those days.  So you've got a guy, two guys who have never been football, never been Millwall before, trying to infiltrate, as you say, one of the biggest firms in the country.  So they were aware that the police were looking, they were all using that as a tactic. We double bluffed. So we went in a little bit earlier. So they all then got nicked and we were, so we were still in. So we were sort of, our faces were at that point sort of known, but not. And that was it. That was my cover, which is you've never seen me before. I'm Jim from Wandsworth. I'm a painter and decorator. And the only thing I've got to back myself up is a bit of a business card. That was it. So what did you do then? What was the first day? How did you manage to get enough of that? Obviously, I'd imagine it'd be tight. Like all top boys are not daft. They can smell corpus or they can smell someone. There was a real big, heavy meal wall pub. And we started going in there at lunchtime. And we're now painting and decorating stuff and got in with the barmaids. We did that all the way through the summer. The first game of the season, we went to the pub. Everyone turned and looked at us. And because the barmaids knew exactly where we were we'd been going in there for the last three months, every lunchtime. Saying we were working around the corner. And Jim, how are you? Come over, usual and all the stuff.   How long did you do that three months in? Just to kind of get an end and just get your face known and... Every, and then the odd evening.  What was your first game like you went to? So the first evening out is probably more prevalent than the first game.  Was that a game or was that just a game? So it was the Friday night before the first game. So the first game was Leeds Away. And Leeds are a top firm as well. So Leeds are a top firm, we're going away. And we were a little bit green.  I can assure you. So we'd gone out the night before. The guy I worked with, nicest man in the world but didn't do his own work. Didn't really want to be doing the job but knew it was a career move. So did. Hated it actually. And we went out and I'm dressed in what I would consider to be sort of mingling clothing.   Went into the pub. It kicks all off.  First night out. Disaster. We get back to the station. I walk in with the sergeant.     And he thought the sergeant had nicked me.  And he went, but you look like them.  That's the idea, which he doesn't.  So the next day we turned up at the Houston to go to Leeds on the football special and we're sitting there. And you can hear there, no one likes us coming up through the stairs at half seven in the morning.  What did they do? I just went over and confronted them, really.  I said, he's married to my sister.  I went, that's him.  He went, ah, okay, fine, fair enough. And we got over it. And then we got on the train and then we met the four guys that we then, well, you know, it was used as probably the right word. The four guys that then saw us through to, well, three guys that saw us through to the two and a half years that we were doing it. He weren't football hooligans as such, but they knew everyone that was and they were well respected. One of them was really well respected. What was it like having the first tear up? Could you get properly involved? Did you have a free pass to get the first tear up? Well, the first tear up was the night before, which was that, that came down to self-preservation. He came out of it a lot worse than I did.   Which is what you never do.  Unfortunately for us, the bouncers stepped in pretty quick and threw us out. But in that instance, it was just self-preservation. So you just do what you can in order to get yourself out of that situation. But the actual first time was Leeds that day. What was that feeling like?       We went in, walked up steps and it's the first time I'd experienced there's 1500 Millwall there.  It just came up over the things that no one likes.  How many of them were active out of the 1500s? So the thing about some clubs is there's a hooligan element in most football clubs, if not all. But certain clubs have a reputation. So someone like Tottenham, let's say, would take 5,000 away. There'd be 400 up for a row. And the other 4,600 would want to watch the football. With Millwall, there'd be 5,000 away. There'd be 400 up for watching the football and 4,600 ready to have a row if they needed it. Is that why they get the reputation that they have? They just have that. They're just passionate about their club. I'm not saying that the other supporters aren't, but they have that mentality. It's like West Ham, it's like Chelsea. It's like a number of clubs. It's different now because of the way the football works and the amount of money that's now in it. But it's still there. But it was at that time that whoever we took away, you knew that there was a large proportion of the people that were away or at home.  I had Bull Gardener on. He was West Ham top boy. And he says, is it tiny? Because tiny wanted the phone bill.  And Bull phoned them and they took them and sorted it out. But that was to the top boys from obviously Millwall and West Ham.   Yeah, of course, but it was dying. And ultimately, obviously, there was a time delay. There was a time difference. Things had moved on from there. And good for him because it comes down to respect for another human being, doesn't it? So I can understand why he would want to do that. But I can also understand why he would have got a lot of stick.  Did you have to go to every game after that? Every game. So then where did you draw the line from?  It becomes what? How did you find the balance? Was it hard? I get asked this a lot.  It was just a job, mate. It was a job. I was 21. I was a stepping stone for what I thought was going to be a long and successful career. And so I just looked on it as a job. And my job was to be as convincing a football hooligan as I could be. And so I was going to make sure that I was as convincing as I could be. And I ain't going to be a convincing football hooligan in the family enclosure eating ball suites. It's not going to happen. So I just immersed myself.   Yes, if you want it, if you let it. But it is a job.  When did you realise that you had a name? When did you feel accepted? How long into the job? So we were going to the pub that I mentioned earlier and we sort of having conversations with the landlord and he had a load of garden furniture nicked from the outside. I'd say load, two tables and six chairs because it wasn't massive outside. And then he realised he'd done it and the van came past and he ran out and confronted them.   And I was there and from then on I had a really, just had a really good relationship with him and as a result of that, yeah, that's when I came out and went, yeah, we're getting somewhere now. Was your cover ever blown? Do you see them in your undercover? Do you still get to go to the station or is it just phone calls or private meetings?  We were working above the police station in Broccoli for the first six months.  All of our targets are local to the area. We can't do work. So then we got moved to Hiver Green where we worked for a year and then this was a massive office that was all security camera because it was the child protection, the old child protection offices. And then we got moved from there and actually went into a house that had been provided by the security services. Don's ever trying to interrogate you? One of the top boys, that was something for sure. They were just, okay, one of the lads obviously as time goes on, the trust grows. Yeah, and if you don't give them reason to do that, we got fronted one day, the sergeant said, let's say in slip, that he shouldn't have done and told him where we were working, where we were working. Our cover was, we were doing outside. I had a house that I was doing up with a girlfriend at the time and was doing the work on it.  Never heard of them.  And we had two options, we had the runaway which wasn't an option and there was only one exit and there was six people between me and the exit so I just went on the defensive. What's the scariest moment being an undercover hooligan? Two.   And the second one was Arsenal North Bank as a Millwall supporter in the Arsenal North Bank which is their home end. How did you end up in there?  What was our method then that was that the plan to go on the way and just cause it?  Did you get respect from my wall balls after that?   I said well I'm thinking what do you think and he just went why don't you write the you know write about it write the book so it was 2012 so I went yeah right so we also wrote it and it got um he got picked up and then books like that normally come out and level up coffee tables and things to be fair who was it reading the book to bring back a lot of memories yeah and I can remember I remembered all of it to be fair I remember what I didn't remember for the beauty of online and stuff and matches and you can go on and there were specific games that you can remember what you did and um yeah it was a it was quite cathartic really to do that and um but you're nervous when you put something out something because it's you know with a book the beauty of the book is it's not it's not like a film or um or a play or anything like that is you know you do have some control um and no one expected least for me for it to come out and be as successful as it was and then obviously the comparisons came in relation to id and the fact that this guy's just copied the story from id and just like no they haven't copied anything mate his id is that's my story so it's just that I haven't chosen to to talk about it because I was trying to pursue my um at that time my acting career or my ability rather on the fact that I'd had a film made about me before I was 30 but the 80s and 90s it was at the height of the football hooligans like that was the proper years obviously before people started getting six years and eight years and for the feats but what do you think now that the hear stories now is it even gone now?


My name is Dean Felscher. I'm a professor at Stanford University, and I'm glad to talk to you briefly about a paper I wrote for Anka Target called BIM mediates oncogene inactivation induced apoptosis in multiple transgenic mouse models of acute lymphoplastic leukemia. My laboratory has spent the last 16 years studying mechanisms of oncogene addiction. Oncogene addiction is a phenomena whereby cancers can exhibit almost a miraculous regression upon the inactivation of a single driver oncogene. In particular, we've studied how cancers can be addicted to the myconcogene. Myc is one of the most commonly activated oncogenes in human cancer. Previously, we've shown that when you engineer cancers that are driven by the myconcogene, that turning off the myconcogene can lead to a remarkable regression of these tumors associated with a dramatic induction of apoptosis. But until very recently and until this specific publication published in Anka Target, we had not described the exact mechanism. The work I'm now outlining for you was performed under leadership of a senior postdoctoral fellow in my lab, Yulin Li, with the help of another fellow, Anja Deutschman. He also had help from a former graduate student, Peter Choi, and a former fellow in my lab, Alice Phen. In this work, we found that in a variety of oncogene-driven models of acute lymphobastic leukemia, that shutting down the oncogene that drove these cancers led to apoptosis caused by a specific apoptotic regulatory protein, BIM. Now BIM has been well known and characterized to be a major regulation of apoptosis, but only until very recently has it been suggested to play a role in therapeutic apoptosis. Previous reports have suggested that some targeted therapies may work through the BIM oncogene, and this suggested to us the possibility that this may be a more central regulator how oncogenes maintain survival and regulate the absence of apoptotic programs. What we found is in a variety of different models when you turn off MIC or ABL or the RAS oncogenes and tumors undergo apoptosis, this is causally dependent on the BIM apoptotic regulator. Now what's important about these results are several things. First of all, they suggest that there may be a common mechanism of oncogene addiction associated apoptosis, and that BIM is one of the central regulators of this process. So this provides a novel mechanistic insight. But second of all, and perhaps more importantly, they suggest that therapies that target oncogenes, in particular for the treatment of leukemia and lymphoma, that their efficacy will depend on the ability to induce the safe apoptotic program, and thus we've identified a biological marker of successful therapeutic action. But finally, they may suggest new ways of thinking about therapeutic development. So targeting this program and being able to restore this apoptotic program may be a very effective treatment for particular types of cancer. Now this work focused on the study of models of leukemia and lymphoma, but we think these results are likely to extend to other types of cancer as well. Thus, we found in my laboratory evidence that solid tumors caused by driver oncogenes such as MIC also will undergo apoptosis when you turn off the MIC oncogene. We recognize, however, that the mechanisms could be more nuanced, that BIM may not be the only key apoptotic regulator, that different kinds of tumors may utilize different apoptotic programs, and that the magnitude of the activity may depend very much on specific type of tumor. Current efforts in the laboratory are to attempt to identify the precise mechanisms by which these apoptotic mechanisms regulated, and we're conducting screens for therapeutics that may be able to mimic the effects of turning off these oncogenes and restore these apoptotic programs. I'm excited to continue this work that has led to a very productive and exciting insight into the biology and pathogenesis of these cancers.


Runners may have a more than 75% reduced risk of getting kidney cancer. At the same time the Affordable Care Act, also known as Obamacare, readys for implementation. There may be bad news for some kidney patients. A study shows two kidney cancer drugs are equal in prolonging survival. But what could this mean to you? I'm Bill Brough with the Kidney Cancer News Special Report. Here's a health benefit you don't hear about every day. According to an article in Runners World, runners are much less likely to contract kidney cancer, this according to research to be published in Medicine & Science & Sports & Exercise. For this study, Paul Williams, PhD, analyzed self-reported information on exercise and self-reported diagnoses of kidney cancer. Williams found that his activity level increased, the chances of having kidney cancer decreased. Among the most active segment, those doing the equivalent of 15 or more miles per week, the risk of kidney cancer was 76.3% lower. A good reason to get moving. At the same time, key provisions of the Affordable Care Act, also known as Obamacare, are set for implementation. The Centers for Medicare & Medicaid Services released a proposal to cut Medicare's end-stage renal disease program by 12% starting next year. That number has since been slightly scaled back, but it's going to be harder and harder, particularly for treatment centers in rural and small communities to stay afloat and continue to provide service for patients as cuts are made. This according to Deborah Pritchard, a kidney cancer survivor who relies on dialysis. These cuts in Medicare may spell bad news for people dealing with kidney cancer. According to an article in Health Day News, the drug Pozopinib, or Botrien, works as well as Sunitinib, also called Sutent, for treating advanced kidney cancer. But a new study finds the former has milder side effects. This new trial was a head-to-head comparison of Sunitinib and Pozopinib. The researchers found both had similar safety profiles and survival benefit, but there were milder side effects with Pozopinib. According to lead researcher Robert J. Mozart, an oncologist at Memorial Sloan Kettering Cancer Center in New York City. Dr. Mozart said, and I quote, the data also suggests that patients on Pozopinib have a better quality of life. Both drugs cost about the same, around $6,500 per month, and are covered now by Medicare and many private insurers. I'm Bill Brough, and this has been a kidney cancer news special report.


So thanks, Bill. And I'm going to be giving the next talk just to give everyone a brief overview of the UDN. We had a pre-meeting webinar which went over some of this information as well as some information on the Common Fund, as well as talking to folks about the Phase II planning process, the results of a request for information that we put out, as well as some of the goals for today's workshop. So as I just mentioned today, we're going to be talking a little bit about the undiagnosed diseases network, the Phase II continuation, the RFI and today's workshop. Just to start off with, the undiagnosed diseases network grew from the undiagnosed diseases program at the NIH Clinical Center. We now have seven clinical sites. They are located at Stanford, UCLA, Baylor College of Medicine, Vanderbilt, the NIH, Duke, and Harvard. We also have a coordinating center, which is at Harvard, two sequencing cores at Baylor College of Medicine and Hudson Alpha with a partnership with Illumina. We have a model organism screening center, which is at Baylor College of Medicine with the University of Oregon, a metabolomics core at Battelle Pacific Northwest Laboratories with Oregon Health and Sciences University, and a central biorepository, which is located at Vanderbilt University. And so these make up the 13 sites that are part of our new undiagnosed diseases network. We also have three main objectives for the undiagnosed diseases network. The first of these is to improve the level of diagnosis for these previously undiagnosed patients. The second is to really facilitate research into the etiology of these often ultra rare conditions. And then third, we want to really bring together the clinical and research communities in order to be able to better serve the undiagnosed community. This just gives you an idea of where we are as far as our funding at this point in time. We have now awarded all of the major sites that are going to be a part of the undiagnosed diseases network. We do have one last batch of R21s, which are yet to be awarded this summer. And it's likely that there will be a couple more supplements that are made for doing some gene function studies and other needs of the network. But there will be no additional sites awarded during this first phase of the undiagnosed diseases network. As mentioned already, there's been a big focus on data sharing and outreach in the undiagnosed diseases network. The manual of operations, which lays out all of the network-wide protocols for the UDN, is already available on the Coordinating Center's webpage. And you can find that here. This manual of operations is updated every time we have an in-person steering committee meeting, which right now is three times a year. So every couple of months, there will be a new version of this manual, which gets posted online. And the old versions are all archived there, so if you've looked at a previous version, you can see where the changes have been made. We're also really focused on making the data available. All of the data that's collected as part of the undiagnosed diseases network will be shared. Some of this data will be going into DBGAP. We're also going to be sharing data as part of Phenome Central. So all of the sites, as Bill alluded to earlier, are going to be collecting phenotypic data using a program called Phenotypes. This information can then be shared through Phenome Central, which allows for matching and for us to become a part of the matchmaker exchange, which is really set up so that a number of these different database nodes can share information about patients without you having to put your data into multiple different databases. So by having all of the data from the undiagnosed in Phenome Central, individuals that, for example, went to Gene Matcher would be able to tell if there was a match with the data that we have in Phenome Central. Just to give everyone a brief overview of the undiagnosed network-wide protocol, all applicants to the undiagnosed apply to a central online application process that's housed at the Coordinating Center's website, our undiagnosed gateway, we call it. And all of the applications come into this gateway and are then routed out to all of the clinical sites using an algorithm. For the most part, they are routed to the site that is geographically closest to them. And this is really due to the fact that when we initially established the UDN, one of the main factors behind expanding to a set of multiple different sites was trying to make it easier for the patients to be able to access a center that would be able to provide this undiagnosed evaluation. Once the applications have been referred to a site, they are reviewed by the clinical sites. This just gives you a breakdown of how many applications have been seen at the extramural six clinical sites versus the NIH UDP. The NIH UDP site has a higher quota for patients because they were already seeing approximately 150 patients per year. The clinical sites were ramping up from starting at 25 patients which were done as soft launch patients known to the sites and working up to seeing approximately 50 patients per year by the end of FY17. Once they do their in-house review, the patients that they would like to accept are brought to a case review committee meeting. This group meets every couple of weeks and is made up of clinicians from all of the clinical sites. They discuss the cases and cases are accepted into the network. The cases that are accepted sometimes then go for the clinical evaluation first. Other times some of the sites are doing the sequencing first. But this just gives you an idea of approximately how many clinical evaluations and sequences have been completed as of the end of February. The online gateway process for the undiagnosed diseases network just opened in the middle of September of 2015. So this is only a couple of months worth of data with the entire UDN 13 sites being available. So now I'd like to tell you a little bit about the phase two continuation process that we already heard about from Eric and Walter this morning. So the common fund right now we're starting the phase two continuation process for the undiagnosed diseases network. As part of this process we put out a request for information with the responses due back in December of 2015. I'm going to give you a little bit of a summary from what came back from that RFI. We're then having today's workshop to be able to get feedback from all of you about what potential needs gaps and opportunities are for phase two of the undiagnosed diseases network. And then a third component of this continuation for our proposal will be an environmental scan where we really look at what's out there in the community and how does the UDN uniquely fit in. And so today feedback is really the key. We want to have lots of discussion with everyone. And for today's workshop we've invited a number of different types of folks as we went around and did the introductions you likely heard that there are a number of UDN investigators in the room as well as outside experts. We've invited some of our external scientific advisors who are regular advisors to the undiagnosed diseases network and program staff are all here to be able to attend this discussion. What we talked about the main goal is to assess these needs gaps and opportunities. And throughout the day there are going to be a number of different roles that you'll hear about as we start going through a set of six questions. For each of these questions we're going to have one of the program staff act as a framer and set up what the question is and what we're planning to discuss. We'll then have a brief presentation from one of the UDN investigators, another brief presentation from one of our outside experts, and then we'll have a moderated discussion with a summary at the end. We're also going to have a panel session which by panel we mean we're going to have a bunch of people talk about topics that weren't necessarily covered by the six questions. These will be brief five minute presentations and we do have two slots left that we can fill within that panel time. So if something comes up during today's discussion that you think of but that doesn't seem to really fit with one of the six questions that have been outlined please just send me any more or catch me during one of the breaks and at lunch we'll send out assignments for those other two slots if there are some topics that have come up. Otherwise we will just use that time for further discussion. Now to go on to the results from the request for information. This is the request for information that we put out. The replies were due back on December 11th. And these are the questions that we had in the RFI. First we wanted to know what are any of the key issues that were really limiting undiagnosed diseases research and the clinical and laboratory evaluation of these undiagnosed patients. Second we wanted to hear about any new ideas or strategies for being able to improve upon the undiagnosed diseases network and undiagnosed diseases research. Third we wanted to ask folks about any ideas for criteria or metrics for looking at undiagnosed diseases research. How should we be evaluating this so that we know what success looks like. And then finally we had an open question for any other ideas that folks thought might be relevant to undiagnosed diseases research. And so this is just a brief summary of some of the responses that we received. And in the topic of new strategies we heard folks talking about wanting to address more non-genetic causes of undiagnosed diseases that we should think about what the course of action would be after sequencing. So what other novel methods could be applied to these undiagnosed patients and really making sure that the data that's produced gets released in a timely manner. We heard from a number of folks about increasing the role of patients and families as well as encouraging international collaboration that with these rare and ultra rare conditions that it was very important to think globally not just within the United States. There was also a call to evaluate the incorporation of other omics technologies and to consider systems biology approaches. And so hearing these different new strategies this really helped inform the six questions that we're planning on discussing today. And so this just gives you an idea of how each of these topics that came out of the RFI maps into the six questions that we plan on discussing. We also had a number of limitations that were pointed out for undiagnosed diseases research. One was the just limited availability of a healthcare provider to be able to have the time to really sit down with a patient to do a more thorough clinical evaluation. Another limitation that was pointed out was that there are often an insufficient number of specialists especially within genetics and that many of these specialists are not necessarily locally available to patients that they often have to go to a larger academic medical center in order to be able to seek specialist care. There was a call for more rapid diagnostic processes and that there were really some barriers for patients being able to access care. That there was potentially a lack of proper information and consistency. That it was sometimes difficult for these patients to be able to have the financial resources or to be able to get insurance coverage to be able to see specialists. There was also a lack of a systematic method and best practices for being able to validate candidate genes that they saw as being a real barrier to undiagnosed diseases research in general. And a real need to be able to bring together informatics into the discussion as well. And so these topics also map to the questions that we're looking to discuss today. In the criteria and metrics, there were a number of different parameters that were common amongst the responses. One of them was clinical parameters where there was a call to be able to measure the number of diagnoses that were made per various different parameters. So using sequencing or in a given period of time. As well as a real call to make sure that we were comparing like to like in that many of these patients that are undiagnosed have often been to many clinics. And because of that, we need to make sure that if we're looking at how long does it take to diagnose them and the resources involved, that we understand that these cases are very difficult to solve and not necessarily the standard case that would just be coming into a general practice unsolved initially. There was also a call for genomic evaluation metrics looking at the number of variants that were confirmed and new correlations with disease. Metrics that looked at the impact on the diagnostic odyssey. So what is the economic impact of a diagnosis as well as what is the average length of the diagnostic odyssey and how many different specialists did a patient need to visit in order to be able to make a diagnosis? And then finally, there was a call for some more qualitative information to be collected as well, such as survey information on patient reported outcomes. What different changes in care were made once a patient had a diagnosis? And if there were any coverage changes in the testing that was offered to patients as a result of the research that was being done as part of the Undiagnosed Diseases Network. There were also some other more general concerns that were brought up that seemed to be more concerns related to the practice of medicine in general or clinical research, such as that the proof of etiology requires more readily available functional studies when you have a new variant. That having a very diverse electronic medical record system in the United States makes it harder to share data. There were some concerns about being able to share particularly identifiable data and potentially people being concerned about HIPAA protections. And there was in general call to support there being phenotyping standards in order to be able to share the data more readily. And so finally, I would just like to point out some of the questions that we're going to be talking about today. We have selected six questions for general discussion during today's workshop based off of the responses to the RFI. The first of these topics will be the intensive clinical evaluation. Second, transitions of care, third, patients and family partnership. Fourth, training sharing and collaboration. Fifth, the virtuous cycle and integrating data. And then finally, we'll end with moving the UDN forward. And so this will be more of a summary type of discussion. After all of these six questions, we will then have some time for the panelist discussion. And then finally, we'll have a discussion about prioritizing the opportunities at the end of the day. And with that, I would like to thank all of the members of the Common Fund UDN Working Group, especially those who are highlighted in blue here, which are the program team that meets weekly that really were essential to being able to pull together this agenda today. And thank you all for coming. And with that, I'll take any questions that folks have. On your summary about the patient applications, the online applications, how does that number since last fall compare with how many you would have applied to NIH intramural UDP historically? So we're pretty comparable to what the previous application rate was. Bill, do you want to comment any more on that? We were seeing, we were getting applications of about, so we accepted 150, about 600 a year before. And now we're getting more applications than that because we have twice as many spots to fill in terms of acceptances. Instead of 150, we're supposed to fill 300 this year. So, and we're accepting, I think, at a slightly higher rate, partly because the new clinical sites are taking some of their own patients. That is not from the broader national community. But we're still, let's say, we're online on target with respect to the number of acceptances, which is essentially 150 at the NIH in a year and 25 of each of the other six sites. So I would say it's comp, we're getting a few more applications than we did before. But I think the year, you know, underneath your question is one of, you know, sustainability in terms of applicants now because, essentially, this program is destined to triple the number of patients seen around the country. Can we see triple as many really good patients as we did in every previous year in the UDP? I think that in a way that remains to be seen, but we may need to do some advertising for that. Okay, yes. So along the same lines, there are patients that you chose not to see, undoubtedly, that maybe could have been seen and would have benefited. Are you seeing people reapply? The answer is yes, we're seeing people reapply. But let's say when I see some of these cases, I'm pretty satisfied with our previous rejections or not acceptances, as they say. Thank you. So I haven't felt really terrible about most of the cases. I'd say there's only a very small group that are questionable, like maybe 5% or so. Yes, ma'am. Is there a standardized approach to the acceptance? I mean, is there a protocol or some kind of guidance that the different sites are using? Do you know about the variability in that acceptance? Well, every other Thursday, every patient that's desired to be accepted by a clinical site engages in a conference call, at which there's a committee that listens to those cases and they're presented for three minutes or some such. So there is a little bit of purview over that. And the cases, in my opinion, have been spectacular so far in terms of acceptance. But who knows, that might change. And the answer is no, there's nothing that's hard and fast or rules, but there's some general principles, things like have to have objective findings. It helps if there's a couple of siblings involved to family members and things of that nature help us. Any other questions? Yes, Eric. Yeah, actually I was wondering if the recruitment at the UDP and maybe if we have enough statistics for the UDN reflects the sort of general ethnic composition of the United States. And I'm curious because I've noticed at our site it's the patients that come locally that where are patients that do reflect it. But those that come from the gateway, they're more likely to be Caucasian and et cetera and not very reflective of the general Ellie County at least population. This program has never reflected the composition of the United States in terms of socioeconomic or ethnic groups. We see some minorities, but I must say that in order to be eligible for a program like this, one has to have a significant workup at a tertiary medical care center. And that is not provided in our country to poor people. And the UDN has taken some steps to try and make this easier for patients, but we do have to know that they are out there first. For example, we do have a partnership with Nord where we have a patient assistance fund which can help pay for some testing for patients that we think would be good candidates for the undiagnosed diseases network, but that have been unable to get that type of testing at a tertiary care center previously because of health insurance type of concerns, but it is a concern going forward. We also have translated all of the consent forms into Spanish in order to be able to try and make it easier recruiting within Hispanic populations within the United States as well. Okay, so we're pretty much at times, Cindy, do you want to make a quick point? Okay, then I would like to introduce Brendan Lee who is the PI of the Baylor College of Medicine Clinical Site and he will be speaking to us today about some early patient experiences as part of the Undiagnosed Diseases Network. Thanks, Brendan. Thank you.