The Most Complete Computer Simulation of Human Physiology

The Most Complete Computer Simulation of Human Physiology

Tom Coleman, a graduate student at the time, developed a mathematical model of the human body that demonstrated the role of the kidneys in controlling blood pressure. The model has since been updated to include over 10,000 variables and parameters. It is used to study different pathologies, such as hypertension and obesity.

We're going to go up to hemorrhage which is the tab all the way at the top it's bleeding at 100 mils a minute of milliliters a minute and we turn it on we'll go back to chart and we'll go for15 minutes and what you see during this period of time is that there's a falling blood pressure there's a reflux increase in heart rate which is what you would expect we went for another five minutes and you can see that it's actually blood pressures tends to fall a little bit so let's not go look at some of the underlying things that take place first tab is actually blood volume which shows you that you're actually losing this blood volume over a period of time the second tab looks at nervous system which is the sympathetic nerves which actually work to constrict the blood vessels in your body to try to maintain your blood pressure you can see is the nervous activity is going up so hopefully we can increase our blood pressure the third one is actually what's called norepinephrine which is also released from your nerve endings and your from your adrenal and the whole purpose again is to contribute constrict your blood vessels so one of the consequences of constricting your blood vessels is that you limit flow to particular organs you essentially make it less flow go there so what you see is

if you go look at what's happening with with the gut under splanchnic circulation you can see his flow is going down two things you have to protect the heart and the brain with hemorrhage those are the two things we can actually go up to the top and last look at what happens with the kidney and that's actually going down also so this is what we this is what the model looks like in terms of using it from day to day so what do we use it for we actually use it for education the challenge with that particular thing I showed you it is extremely complicated students get lost they don't know where to go look so what we've done is we've actually created a site called just physiology and we'll give you a little bit of a demonstration with that we actually have a patient called Mrs. pale she gets dizzy when she stands up I have the weird names I put in for that so we can actually we limit what students can see we'll go ahead and do a simulation for ten minutes and this is all running on Amazon server so students can do it whenever they want to and what you'll see is we give a normal blood pressure and everything looks pretty fine over just the next couple of minutes while the simulation goes across at ten minutes what we will do is we will turn it to where she's standing up and this is a very simple thing again go for ten minutes and what you'll end up seeing is her blood pressure Falls dramatically. she gets a reflex increase in our heart rate but you can see it's going down very low and so therefore she has a problem clinical problem there are some options over on the right we're not going to go into today which we could treat her to try to prevent her orthostatic hypotension we actually use this with medical students to hopefully understand what disease states what appropriate treatments are and if there are problems for them to learn it in this particular case then not with their real patients the second thing we use it for his research and this is I'm gonna give you a little bit of a study that was done by a colleague of mine he was working on a device that was very similar to a pacemaker and it actually worked like this the pacemaker ended up working through some factor would stimulate the nerves and you would actually end up with a decrease in blood pressure turns out it worked extremely well the this was the basic physiology design idea behind it was that the nerves were involved so what he did was he actually surgically removed the nerves that went to the kidney which was very important even move that and what he got was this is exactly the same fall in blood pressure so he was sort of in a conundrum he said okay this is the way I think it works I removed that factor it didn't work so the next slide actually shows you that's his experimental design and everything in red was when he turned the pacemaker on and you see the blood pressure fell for this couple week period and as soon as you turn it off it comes back up to normal so we started thinking about this is that well let's use human and run the simulation and see what weapons so when you run the simulation we got exactly almost the same response this was actually when we blocked the nerves so therefore what ended up happening was we went through and dug through the model and dig a little bit of exploration to figure out what was going on and what we found out was there was a hormone that nobody had really thought about we knew it went up we knew it changed but how what his importance was suddenly came to the forefront and this goes back to the point is that we have very redundant systems inside our body if we didn't something one thing goes wrong we wouldn't live very long so there are lots of these systems they didn't write together so that's one of the values that we have in terms of using this particular model of human physiology to try to understand these redundancies so the last thing is we're working on and this is probably more exciting than probably anything I've done in my last 30-something years of being a faculty member so we're looking at using the model for what's called in silico clinical trials so if you think about this there are a lot of clinical trials that are going on whether it's for a device to treat something or whether it's for a drug to also treat something but looking out at this audience we are not alike we all have different makeup whether it's our genetic whether it's our diet whether it's our lifestyle it really is a big challenge to try to figure out how each of us would respond to the same treatment and in fact if we gave all of you a very simple treatment such as maybe a diuretic we were half people that would respond with a big response some people that would respond with a very small response or not at all so how do we go about looking at that so what we have done is develop the ability within human to create virtual populations virtual patients if with the sufficient computing power we could do 50,000 we could do a hundred thousand we could do a million patients that are all different from each other and so what happens is we want to use the in terms of helping with clinical trials to understand those patients that would respond to a treatment whether it's a device or a drug and more importantly those people that do not respond because if you have somebody that doesn't respond it's not a value to treat them with that particular device and especially if you're trying to do the clinical trial it's better if you don't have them or know who those people are so therefore you don't include them in your trial so we've tested this a little bit we've actually had some work with that we've got interest from the Food and Drug Administration and a particularly a medical device company so we did a very simple clinical trial we generated 2,000 patients with site with hypertension and we use this treatment that is actually in development we simulated a treatment which is essentially a something that removes the nurse from your kidney and what you see here is the percentage of patients is on the y-axis and the pressure drop so you can see anything to the right of the vertical line is good their blood pressure dropped these were patients that no medication would drop their blood pressure you got big drops in blood pressure the problem is what's over on the left of the line that number so you actually have patients and this is actually happens in the real clinical trials whose blood pressure goes up so here's a device that you don't know who's going to respond and in some patients you actually get an adverse effect so this is where we're going now in terms of using our computer simulation to help with like in silico clinical trials so what I've hopefully presented you what is the most complete computer simulation of human physiology a little bit about what we use it for the clinical trials at the end I'm very lucky for to be following up on the vision of dr. Coleman and dr. Guyton started 50 years ago looking at doing this and I also have some very good colleagues dr. John hall dr. tom lamar dr. Drew Pruett dr. John Clemmer, who helped with this project, thank you for your attention.