I'll be telling you some of the work on how we started with an NSF Eager project on building a genome for a critter known as the 13-Line Ground Squirrel, and that how led to a new early-stage pharmaceutical company started by three of my postdocs. Much of the things I've been interested in are now being pursued in the private sector, including work in the direct-to-consumer space around how we begin to think about the use of genetic data in drug discovery. A lot of work in comparative genomics, so I'll tell you the story of FanaBio, which is the company that we spun out of Stanford. It turns out to be the second company from an Eager that we've started. There's a dog genetics company called Embark that was started in part based on some work we had done along with Lane Ostrander and others in dog genetics. And two brothers named the Boiko brothers that many of you may also know are now at the helm of that company, Edeland Diagnostics, which is a company in horse genetics, and my friend Sam Brooks is here in the audience. She's part of that adventure. And you'll also be hearing some of the work we've done at Dovetail, which is a company owned by Eden Rock, where I'm a director. So highly conflicted, but let's get all that out of the way. So why am I at this particular meeting? So for a long time, I've been very interested in new and emerging model systems for a while. We had a sort of cheeky term in the lab for this called gonzo genomic. So how quickly could we go into a new system, make a genome, make a variation map, and go out after interesting trait? Joanna Kelly, who was a postdoc in my lab, led a lot of this effort. And she'll be one of our speakers later on in the day. She was very interested in extreme biology.  But ultimately, our goal is really to use comparative genomics to inform our understanding of the human genome, ideally with an eye towards therapeutics. So I liken it to sort of GPS coordinates where you've got many different satellites and allow you to triangulate into interesting positions. And really one of the key challenges that I think we face as a field is that as we continue to develop these model systems, unfortunately the federal government can't be the only funder. It may be the funder of last resort, but it shouldn't be the funder of first resort, particularly when these things have economic value. So how do we incubate these ideas and allow them to take a life outside the university? And much of my thinking has been influenced by this book. If you haven't read it, I encourage you to take a look at it. This is Bill Janeway's book called Doing Capitalism in the Innovation Economy, and he sets it up as what he calls the three-player game. So you have investment coming in from early stage by the federal government that really is sort of push innovation. How do we delve deeply into basic science? You then have essentially speculation by financial markets, which is early stage investment. And then you have the true market that shakes this out. And so I'd like to take that as a lens into how we think about this. And ultimately, as I said, our goal really is to move into the world of precision health. And I'm a firm believer that in a world of aging demographic, it is going to be the prophylactic deployment of pharmaceuticals that will avert disease into the future. I'm going to repeat that. In a world of aging demographic, it is the prophylactic deployment of medication that is going to prevent disease in the future. And perhaps the best poster child that we have of this is now the deployment of statins and other medications, particularly in the context of averting cardiovascular disease. Perhaps the greatest success we have in going bench to bedside made use of human genetics. It was the discovery of PCSK-9 inhibitors. This came directly from the work of Brown and Goldstein in understanding the basic science of cholesterol metabolism. And then Helen Hobbs and others really sort of took this on through the study of individuals at the extremes of the distribution. So as we began to study a disease called familial hypercholesterolemia, that is very high levels of LDL, so-called bad cholesterol, we began to understand that over expression of PCSK-9 was one of the key components of this near monogenic form of high cholesterol. And then it turned out simply because of the beauty of biology that if you were born with a loss of function mutation in PCSK-9, you were naturally protected from LDL, not only from high LDL, but also from adverse cardiovascular disease. Regeneron and others led this in clinical trials, and it was sort of a record time or turnaround from the understanding of the biology into the time we had a monoclonal antibody therapy that was being deployed in many people. We can talk a lot about the health care economics of how they got wrong, the pricing, but this is kind of the right idea. Let's look at extremes of the human phenotype distribution and really try to identify medications that can avert disease into the future. Just yesterday, it was announced that the latest in this work has now reached stage three clinical trials. So for those of you who are following this at home, Vennacumab, which is another one of these protective loss of function mutations, just showed a massive reduction in LDL and homozygous FH carriers. These are folks who, unless you put them on this kind of medication very early on, will have heart attacks and strokes at an early age. How do we accelerate this discovery? Well, lots of bets have already been placed. It is now an absolute cliche that data is the new oil. I would argue from a market cap perspective, this is absolutely true. When I was in college, the largest companies in the world were all oil companies. Today, they're all the tech companies. Tech has no choice but to go into this pace. Largely, it is now the largest component of the US economy. So health care now makes up 20% of the US economy, which is why everybody's sort of gunning for this and the idea that you can use data analytics to identify human mutations that are then potentially drug-able is now just a very clear investment thesis being followed by both public-private partnerships as well as the things that we know about in terms of health care systems like Regeneron that have partnered with Geisinger to enable this to happen. So putting this into context, where does the comparative genomics side come in? And this is really sort of the thesis. This is what I believe we need to do far more of with early-stage investment by government and nonprofits. Some amount of bridge funding. So the story I'm telling you today really was an eager grant. One of these things that NSF wants to turn around rapidly. SBIRs, I think, are the lifeblood for many early-stage companies. And that really then leads into placing the right bets. And we will let the market shake it out, right? Eventually, many of the things that are being developed internally then get sold up the biopharma chain. And you just need to look at that structure to understand there can't be too many $100 billion pharma companies. So they have to go through this sort of procession of gobbling up innovation. They themselves cannot innovate internally. So they innovate by allowing the financial markets to place the early bets and then stepping in. So in this context, this is Katie Graybeck, who's in the audience. She was a postdoc in my lab. She came from Sandy Martin's lab, where she did her PhD. And she brought this incredibly cool project, right? So she said, Carlos, I want to study hibernation and 13-line ground squirrels. And as I said, well, that sounds like a really interesting idea. Tell me about it. And turns out that these are critters that can get down to four degrees Celsius, which sounds pretty cool to me, right? So here's what the sort of lifecycle of this little critter looks like. This is the torpor that they go into during hibernation. So here is sort of the early fall. These guys are finishing their bouts of feeding. Then they go down into this almost pre-programmed circum-annual clock near freezing. Every few weeks, they've got to shake off the icicles. And we'll talk about why that's really, really interesting. And then the whole process repeats itself. So not only can we study this through the means of comparative and population genomics, because they are an emerging model system, what made this absolutely possible was NIH investment in being able to do experiments, right? So this isn't just an observational project. You can actually go in and carefully record all matter of life history for these critters. They can go into hibernaculum that you can do experiments, time, and begin to study how the variation actually plays out. And we'll talk some about why this was just really critical to getting this project right. So again, to sort of set up the biology, these guys are feeding, feeding, feeding all up into the summer. By this point, when they begin hibernation, they switch from glucose to lipid metabolism. There's absolutely no feeding, obviously, while they're in hibernation. And again, the sort of cycle repeats itself. So this really is a very, very interesting cardiometabolic phenotype to study as you're switching. And the question becomes, what could we learn from this? The other thing that happens, which we'll return to, is that hibernating animals are some of the only animals that we know of that can have neurodegeneration. So when they go into hibernation, they actually prune the dendritic tree, lose many of the neuronal connections during these bouts of interarousal. They actually redevelop these in a massive effort. And so the goal is, can we also potentially study this for some of the phenotypes of greatest interest, which include really the pressing issues with neurodegeneration. And as many of you know, billions and billions of dollars have been thrown at Alzheimer's therapies, none of which have really made it to market in any successful way. So the first thing we did was try to improve upon the existing genome assembly. So working in collaboration with Dovetail Genomics, which has one of these high C and high C-like products allowed us to dramatically improve the quality of the assembly. So we've now got hundreds of megabase scaffolding on which to hang much of this work. We then develop the kind of genotype bi-sequencing strategy one needs to generate markers all over the genome. I don't want to tell you about that, because it's now sort of a trend of true technology that many of us can develop. But there's just a ton under the hood here that I don't have the time to tell you. The goal, of course, was to take and ask questions about the inherent biology. So here is some variation from critter to critter in when they go into onset of hibernation. Here's a structure plot for the critters one has access to. And of course, there's tons of population structure, which is both good and bad when you're trying to map as many of you know, but you want to make the best use of the scenario. And in our case, given our expertise in high level models that can take into account both local structure and global structure, we were able to really use this to get at some very interesting biology as part of this NSF grant, including the top hits that are driving this sort of seasonal onset of hibernation. Many of these are, of course, in the pathways that you'd like, including feeding and insulin response and many of the traits that you'd, of course, want to try to go after. So from the point of view of the NSF, we had promised that we'd build a better assembly. We'd build a genome map and begin to get at the genetics of the trait. We were able to demonstrate timing of hibernation is heritable, much of the variance explained by a few loci. Many of these loci cluster in the genes that you'd be interested in. And the hypothesis that a multi-omics approach would allow us to get into potential biological pathways that would be potentially druggable. So at this point is where the story got very interesting, having the privilege of mentoring just extraordinary folks in the lab. I had three colleagues who decided they wanted to go on an adventure. And so three of the postdocs got together and said, there's something potentially really interesting here, put together a business plan, worked with a local accelerator, and got half a million dollars in funding to take this to the next stage. So the company's now led by Ashley Zender, who is a DVM PhD with expertise in cancer biology. She's founder and CEO. Katie, who is our expert in hibernation biology, is the chief science officer. And then Linda, who had worked with Eleanor and had been a postdoc at the Broad, leading many of the efforts in the Malian genome project, spent some time in my lab as a postdoc and then joined the company as CTO. And I think it's just been an incredible founding team to get this off the ground. The sort of investment thesis behind the company is that the huge array of interesting biology that gets explored by mammals could very well be what we need to sort of improve the bets that get placed in pharma. As I mentioned, the PCSK9 story told us that the genes that predict LDL cholesterol also predict early heart attack. So it begins to tell us how we might be able to make these investments. The contrast is that the genes that predict HDL don't predict MI. Five different drugs went to market because they were able to target LDL lowering and improve the clinical endpoints. Five different drugs failed in clinical trials. They were able to raise HDL, but they weren't able to make any movement on the clinical endpoints. So if we could add on top of this the comparative mammalian approach, this could rapidly accelerate. The argument is that human genetics maybe gives you a 2 to 3x improvement on placing the bets. How much could comparative mammalian genomics get you? Could you get to a 10x improvement and dramatically reduce the cost of bringing these pharma pseudocals to market? It's about a $2 billion in 10-year process. So anything we could do to improve that efficiency translates into better drugs for all of us. Hibernators turn out, because of their fascinating biology, to have lots of potential use in understanding diabetes, osteoporosis, ischemic injury, Alzheimer's disease, and many others. And so we began there. But of course, the idea is that it could go in many additional directions. Of course, what we want to take is ultimately a multi-omics approach with great data analytics. And so I would argue if you look at, say, the failure of IBM Watson to bring AI to cancer, it wasn't the AI. It was probably the data. There's only so much you can do from just ingesting a ton of articles.  So maybe if we did this experiment at scale in the way that I would say NHGRI has led the field, the wonderful thing NHGRI has done is continue time and again to invest in these technologies and enable us to do things at scale. We all remember the candidate Gene Winter in the early 2000s, where every week there'd be a different paper with an irreproducible result. Say what you will about GWAS for the love of God. At least it was reproducible. You could go into population after population and get odds ratio within a standard error, which is exactly what you want to do, and that has led to an acceleration in our understanding of the biology. The same thing is now happening with GTEC and other experiments that do functional genomics at a reproducible scale. So if we think about the opportunity to bring this into the context of industry, as this is getting cheaper and cheaper and cheaper, you're now beginning to build those layers of evidence that may be necessary to break this through. So the idea here is quite straightforward. Let's begin with the ground squirrel as a model system, understand the core genes that are involved in different aspects of the life cycle, and see whether this could be useful in our understanding of the biology we want to punch. Here is part of the tissue bank that was licensed from Colorado. We were able to take tissues at different stages during the life cycle. I'll focus on things that have to do with the late arousal. So this is right when the critters are in hibernation but have sped up their metabolism to shake the icicles. This is also when a lot of that neuroregeneration is happening, so potentially quite useful in understanding potential points to impact for neurogeneration. So, of course, what you want to do is take a kind of approach where you're using clustered gene expression analysis to get at pathways that might be useful, and that's exactly what I'm showing you here. So this is a slide from Fauna, where you're showing over expression in red and under expression in blue of different tissues, different genes in the hypothalamus during the late arousal period, the inter-period, inter-about period, and so on. And then you put this through a tool similar. This is the Brode's connectivity map, which has about one and a half million experiments for 5,000 small molecules and 3,000 genetic reagents in what their expression profile is. So you kind of play the inverse game, let me look for expression profiles that might target the small molecule. And in our case, when we looked at the hypothalamus, it turned out that 11 of the top 13 hits were already implicated in either Alzheimer's or similar in sort of beta-amyloid biology and many of the things that we knew go wrong when beta-amyloid begins to accumulate. In fact, this included the only approved treatment for Alzheimer's, memantine, which we'll talk about in a moment, as well as two new compounds, Fauna 2001-2002, that we've now begun to do some very early stage functional experiments. And I'm very grateful to the team for allowing me to share some of the data. So this is what typical assay looks like. You're putting this into a well-understood cell model for neuron. These are cells derived from a four-year-old patient in the 70s. They were then chosen and differentiated into these sort of neuronal pathways. When you add beta-amyloid, you begin to get cell death, and that's measured by this MTT assay, and then you can begin to rescue the phenotype. In this case, this is with the memantine, which is the approved therapy. And then here's what's happening with the new compounds. In fact, they seem to do a little bit better than memantine, and this is a decreasing sort of dose of the compound. Again, very, very early stage, but it begins to say, boy, there's some interesting biology here. There's ways that we could begin to add onto existing therapies. So this is sort of the logic, begin with whole genome data, add interesting layers of data that then improve our dark target identification, begin to license some of these assets up the pharma chain, and on and on we go as we improve our understanding of the biology and how to punch. And so this really kind of brings us back to the model I set out earlier, the sort of three-player game with the state investing early technology, some bridge funding, until some adventurous venture capitals are willing to put some money in. In this case, it was the age one incubator. In the case of fauna, they then were able to rapidly follow up with a seed round of investment. And I'll leave you with this last slide. It was a $300,000 initial investment in late 2016. It was actually December of 2016 when this was awarded. Less than two years later, age one picks this up with about a 20x increase in the nominal value based on the capitalization of the deal. And then a few months later, a second round of funding with the seed coming in led by TrueVenture gives it another sort of 2x on that. So we've basically gone in three years and increased the value of this idea by about 30 to 40 fold. And in my mind, I think this is exactly what we need to do to begin to take these and let others place the bets that allow the market to then shake out and see what's valuable. With that, I'm happy to take any questions you might have as part of the panel that we're all going on to. Thank you very much. So yeah, so could the speakers come down and sit at this lovely table here in front of everybody?


I'm on the central line today and I'm going right out to the end to Epping. I don't come up here that often but I always enjoy a trip because as you can see we're kind of traveling through pretty much open countryside so it's quite an attractive part of the London Underground from that side it's might go for a walk up there on that hill one there that's quite a nice place to watch for your trains. So you probably gather the reason we're going right to the end of the central line is because we're going to the Epping Ongar Railway which I haven't been to for a while I've called in a couple of times I went on it back in about 2005 when it was a DMU and it had the finished steam loco so I haven't had a chance to ride on it since then so that's what we're going to today. This section of tube line though was originally a railway line which goes under the M25 this is the only tube line that goes under the M25 the only other underground line to go on the M25 is the metro port and once you get past Epping. So the section of line we're traveling on now was opened by the Eastern Counties Railway in 1865 and the terminus was Epping and then its successor the Great Eastern Railway extended the line to Ongar in 1865 sorry this line opened in 1856 and extended to Ongar in 1865 and the Ongar Railway although it kind of carried on was always sort of seen as a bit of a branch and then eventually it became part of London Underground in 1949 I'm pretty sure it was but what happened was the good yards stayed open so steam trains would have still worked along here up until about 1966 they might have become diesel towards the end but probably been at normal now just going to look out here there's a glimpsed London Underground node and it wasn't yellow when I asked and they painted it yellow so it's coming into Epping the Ongar branch would have carried on just beyond the station up there so we won't get to travel on those 100 or so yards of track but we're going to travel on as much of the Epping Ongar Railway as we can so here we are we've arrived at Epping so what happened was once the um so I'll just show you now if you look up here you can see they've put like stops in so trains don't actually ever now go beyond there but beyond the bridge the line to the left is Reverse Diving the line to the right going up the hill that is the old Ongar branch so not particularly so very occasionally trains have still traversed on and off the Ongar branch when they've when they took the preserved stock that used to work on the branch up until it's closed so it closed to public in 1994 it was electrified I think it's about 57 prior to the electrification this line was electrified but prior to the electrification of the Ongar branch London Underground had to hire a steam train from British Rail so steam would have worked through here up until up into the 50s now this station is a bit of an unusual one because there is an entrance there but I don't think it's ever open so this lattice footbridge is inside the ticket marries but the concrete footbridge there is outside the ticket marriage so standing up here we get a nice view of the station so occasionally trains do come in here at busier times I won't go down there because station staff are already looking at me thinking what's he doing on that footbridge so what we need to do now is get out we need to find a bus not only those buses there's a bus that's going to take us to the Epping Ongar Railway so let's go and see where that is so we've got to get out the station first so here's my ticket I've got a travel card I like my travel card because I can get on and off the stations as I wish if I want to just go on the station to look at trains it works it doesn't work with an oyster card so here we are here so as we come out the station now I'm out through the ticket office the bus to take us to the Epping Ongar Railway is due to arrive here so I've just got to wait now for the bus to arrive one and then I'm going to walk across the road so you can see the station building so it'll be quite an interesting day I think they're running a few different trains on the Epping Ongar Railway so I'm looking forward to it so once the bus has arrived and taken us there I'll show you what we see on the Epping Ongar Railway but there we are there's Epping Ongar station so everyone on the bus will take a bit yeah I know who they are now traveling just travel through later north wheel to bought my ticket so this ticket is for the bus and for both trains they're running on the Epping Ongar Railway it's quite scenic out there quite attractive bit of common land so wherever we've come here on the central line which is part of London Underground we are actually out in Essex now we're no longer in Greater London so when you travel to the Epping Ongar Railway by train obviously you go up to Epping like I've done today and then you get this bus so you kind of get the best of both you get a pleasant vintage bus journey through Essex and then you get a train journey when you get to Northwield so I think it's going to be very interesting there so we've arrived at Northwield we actually arrived on the other bus but I went and had a look in the shop and the other bus drove off so when there's two buses out you can hear won't be able to see it being here aeroplanes that's because we are very close to Northwield airfield so there's the gift shop there now it's looking quite exciting I can already see steam in the distance there's that class 37 about where that is there is a little industrial loco built by Hawthorne Leslie called Isabel and she's going to take us for a break van ride up into Epping Forest so we arrive here this is the main part of the station that way is looking towards Ongar signal box and we have a class 47 which I'm really looking forward to arrive behind because that's going to be a winning loco for me so um we just have a walk up here so this is a class 47 with the grape rice lobby on the side so that is the livery of the class 47 which works in Scotland so we're going to have a trip on that later but first we're going to have a a break van ride in this shark break van behind this Hawthorne Leslie locomotive Isabel so I'm really looking forward to this it's a winning loco for me it's also the second locomotive of the year I've had called Isabel the other one was at the Amerton Railway two-foot gauge loco now let's just have another we'll go around that side have a better look at Isabel shows this is part of London Underground in my lifetime how rural it is it's all fields beyond there just beyond the end of the platform was the only public level crossing on the London Underground it was a bridal path which goes off up into the fields there's some more stock up there we'll go and have a look at that a bit later and there's a mark to carriage in Anglia Railways livery of Buffet so I might go and get a cup of tea there later let's go through here you better look at the break van so this is there sitting here and have a cup of tea it's a I just said it's a mark to Buffet so this would have worked between London Liverpool Street and Norwich and the trains were replaced and the mark 3 is there about to be replaced by the Stadler Flirt unit so here's a shark break van I know I did show you this the moment they go but I'll show you again because here we get a bit of even if you look down there that is a ballast plow so when they're dropping ballast that goes down and that pushes the ballast off the rails and into the area between the sleepers so let's just have a look at here's the bell again she was built in 1919 I just read that literally off the work plate and as you can see she's 100 years old still going strong so she's taking people up the hill up there over to the other side of the M11 into our effing forest so we're going to go for a ride on her now getting ready for tomorrow I'm not going to be here tomorrow but for those you visit row tomorrow they're going to be lucky enough to have a trip behind I haven't had pictures at all I had her on the main line between Schupf on Avon and and it's also an oak reach under behind her and there's this plaster it's down here I have to come to one of their diesel events to get that logo for haul if so it's now time for us to go and enjoy our break van ride into the forest um it's a bit cold on the way back but then it is winter so I can't complain I do like a driver's eye view I'll upload that as a separate video from Cooper sale this will handle it just up in the forest back to here so look out for that there'll be another video a driver's eye view from Cooper sale to Northwield in the shark break van I'm now as you can see I'm on a more conventional passenger train sitting in a mark two carriage it's class first you want on the front and it's going to take us up beyond Cooper sale up as close as the railway can go to the boundary with London Underground so looking forward to that so that will be beyond Cooper sale will be a little bit of new track for me and then after that the 47 that we saw when we arrived here is going to take train all the way down to Onga so I'll show you Onga station so when we get to Epping Forest I'll just give you like a view like this out the window so you can see what there is um there's no station so we won't be getting out and then um we'll have a look around the rest of the place and as it has just been Christmas is still beautifully decorated with Christmas decorations so um yeah time for me to have a bit of a diesel bash we've had a steam ride as well though which so it's been a great day so far this is as far as we're going I believe we're quite close to the station um Epping underground station not sure exactly how close but we're at the limit we can go so that's the view on that side just see some houses in the distance if you look over here show you out the window you can see it's all you know fields etc and um looking that way see the whole train so we're now going to travel the 47s holding us we're going to travel behind the 47 all the way down to Onga so now we've got half a half an hour's ride sitting in a marked two coach behind the diesel reminds me a bit of the days when the 47s still work across country trains remember sitting in a train hauled by class 47 and mark twos although they were the air conditions are rather than these ones where you can open the window so yeah we're now going to Onga always enjoy um when you get a drop like window you have to put your hand out like this and open the window not many trains you can do it now so here we are this is Onga station there's the signal box just there there's some carriages here there's an old um seven emu carriage and there's some mark ones here under restoration it's going to have a look at the loco so we've come on the 47 the 31 took us up to near Epping station and the 47 was on the rear and has hauled the train all the way to Onga we left the 31 behind at um northwild so there's a bit of the yard there quite a few carriages awaiting restoration this carriage is a mark one this was the only mark one carriage in our train the rest were there were two blue and gray mark twos and there's um a mark two brake carriage so this is where the old good yard would have been if we go up here past the ticket office we can go and have a look at the at the loco there's the sports here here we are i know we saw her earlier on at um and northwild all train is authentic memory of childhood something but 47's work in the cross country trains with a lot of mark twos so she will run around her train and then um um we will go back to northwild i'm just going to show you something up here there's a couple of other things on display um well i'll do videos in main and europe i sometimes we go to a railway station we find the plinth loco plinth locos don't really exist so much in britain well they do exist but they're rare but here's one here plinth diesel loco i mean in britain i think the main reason they don't exist is a lot of them i looked after and kept running but here's a plinth loco so maybe one day it's like i'll run again it's a little industrial diesel so it's um here quite a nice little gate garden so 47's are going to run around her train she's going to come like literally right up to where we are now so i'm going to let you watch that quite a tight run round look they've got there but they're still some track just there the 47 will go around to the other end of the train they'll take us back to northwild so i shall let you see that judgment here the one in the orange jacket these now are going to change the points so the next train the point is at the next train so we're going to have a wander around we're going to get back on the train we're just going back to northwild back down on the platform a couple of things i want to show you so a moment ago we were up there there's the plinth loco this railway is possibly unique in that it is measured in kilometers and mile posts so all railways when they were built in this country were always built in miles so it has mile posts which are done from liverpool street so just before northwild station you've got mile post 19 i'm not quite sure which mile what the nearest mile poster here would be but probably around mile post 22 maybe but when it came part of the underground it was measured in kilometers and they start here see just there that zero zero that is kilometer post zero and then it's measured in kilometers that way all the way down the whole central line even today the central line is measured in kilometers from ongar rather than from epink so you go that way the kilometer posts kilometers are going up come and coming this way the miles are going up so as we go that way the miles are going down and vice versa and another thing that happened here a loco once ran away and hit the buffers in 1934 as you can see there's a picture of the derailed loco must and yeah bit of an incident happened and there's the rescue operation so let's hope nothing like that ever happens here or anywhere else that matter again right i think i really ought to go and get back on the train because soon the train will leave for northwild but yeah what a lovely country station this is and it's hard to believe even in my lifetime this will part london the ground network it's so scenic when you're between here you know very rural it just doesn't seem like london underground even more rural say than the metropolitan line beyond rickman's worth so right time to get back on train so here we are we're back at northwild we had a very interesting trip up and down the line behind class 47 as carriages are there the loco has now been uncoupled running around ready to take the train back up to ongar it's nice you have northwild station building and i really wish i could have come here though when it was still part london underground it must have been there was just one track through here and the lattice footbridge you see today there was a concrete one which i think had concrete cancer and unfortunately had to be demolished which had been replaced with this one which probably gives it more of the feeling of how the station would have been in its pre-london underground days now here this was the only level crossing public level crossing on the london underground it's not even for roads it's a bridal path you can see it says sign there says public bridal way it goes off into the countryside but as i said i'd like to have seen it here in the days when it was still part london underground well i've sort of got my wish come true london underground train here which is really nice to see just to give that nod to the fact that it was part of london underground network also here something completely different another industrial tankage and i think it's another one built by hawthorne leslie so it's like a larger cousin of isabel who was working the breakdown lines and there's a few other interesting things up there you can probably just see the fumper sitting there number 205 205 there's also a peak class 20 and another dmu i'm going to now cross what was the only public level crossing on the underground because it goes this way there is also a public footpath further up the line so yeah let's cross the track and get a better view of the london underground carriage and you can see the carriages there and the dmu's just beyond the trees so um i'm now going to find my way around to the front of the station to get the bus back to epping and head back to central london so it's been a really great day really enjoyed it here epingongar railway um i've to come back and have a gala on perhaps so um there's the bus oh there's the 47 um and there is a bus as well so yeah looks like my bus is here so from class 47 to the bus it's um time for me to go so yeah thank you very much to epingongar railway it's been a great day really enjoyed it and if you ever you know in london and you want to come out jump on the central line you can get the bus to come here so you don't even need to take your car you can have a great day out on the epingongar railway so thank you very much for watching please do feel free to comment like subscribe tell your friends etc and goodbye