Last year at the Re-Deploy conference, my colleague Dr. Richard Cook gave one of the most cogent and clear talks on descriptions of resilience and resilience engineering that I’ve yet to come across. I’m embedding the video below, but I’m also including an interactive transcript for those who prefer reading rather than watching and listening.
If you’ve at all been interested in resilience and Resilience Engineering, I really do recommend spending the time to see this.
I'd like to begin by thanking Paul and Adrian, Mary, James
of the AV folks here the theater for the work that they've done,
putting together a conference and also trying to set the stage for us.
I'm not going to talk about myself at all because it's not very interesting,
but I will put on this screen my,
my only political statement for the day.
And if you have an interest in my politics,
you can go look up Croixlorraine.org and you'll understand everything.
The title of this talk is a few observations on the marvelous resilience of bone
and resilience engineering. There's a very long,
small print disclaimer here about all the things that I'm not going to do and
the things that I do do and the things that I shouldn't do and that I'm
disclosing here. And a bunch of things about my past again and stuff.
Very interesting. This is a simple talk about complex systems and
most of you are dealing with complexity in some form or other and trying to struggle with, with the consequences of that. And I'm going to talk about an area that exhibits all of these properties, but that is not your home base. I'm going to talk about bone and I think in the end that you will, my hope is that you will come to believe that bone is not a model of resilience or a metaphor for resilience, but the archetype of what resilience is that when we try to understand resilience, the first thing that should come to mind would be bone. And if I succeed today for you in the future when someone says, what is resilience, the example that you will give to them as bone. I'm also going to have to talk a little bit about resilience engineering because the engineering part of resilience engineering is, is a pretty complicated sort of idea and much more difficult to pin down than just resilience itself. Okay. We'll just do those two things. That's it. Nothing big. And because my kids are all in advertising and they're constantly telling me to cut to the chase in conclusion, let me say this
the, the, the bottom line here is pretty straight forward at least about bone and resilience and how it works. bonus continuously remodeled. Many of you probably are not aware of this, but your skeleton is replaced about every 10 years. And that's pretty remarkable because from your perspective, the skeleton is a kind of static thing. It's always there. You have it. And as long as you don't do too many bad things to it, it doesn't change very much. But in fact, your skeleton is constantly being replaced. The making of new bone is in a dynamic balance with the destroying of old bone. And this is a process that's energy requiring and takes place all the time. And because it's happening at this little level, you don't notice it. But if I were going to pick one thing to remember from this talk, it is the idea of this dynamic balance between creation and destruction, which then provides the platform for all the resilience that we see. Resilience is constantly present, it's constantly enacted, it's constantly requiring energy and we are unaware of that because most of the time it's happening in the background and at a fairly little level so that we don't see it playing out. The other thing is that the demolition and construction of bone is directed by mechanical strain. And this is really important because resilience is focused on particular kinds of things in via via various sorts of mechanisms to achieve a specific ends. We'll talk a little bit about repair of some additional mechanisms. I don't want to talk about that in detail. Um, bone. But the other thing is that the system of bone is not just a skeletal system in the sense that it holds us up. It also provides other functions. It's the primary store in our body for calcium and phosphorous, which are both very important minerals and very, very difficult to get from the environment. And important to have. And it turns out that calcium is the most important ion in the body. finally, this idea about resilience is that it's all about signaling. There is no master controller and resilience. There's no high God of resilience, which directs everything and organizes it. In fact, it's a messy layered network that is actually performing these functions and we'll show you a little bit of the network even though it's not yet well understood and there's lots and lots of crosstalk in this network and a lot of cell level integration of the activities that are going on. Cells respond in a way that makes this all possible. bones resilience is what I would call Woodsian. And this is after Dave Woods. Dave Woods has, if you haven't looked at it, you certainly should. The four concepts for resilience and the implications for the future of resilience engineering and reliability engineering and system safety. But basically he's got four different ideas about what resilience is and the last two are the most important. One is this idea of graceful extensibility, that the system has, not a sharp boundary, but a rather soft boundary that that allows extension of its function. And the other is sustained adaptability. The idea that we are constantly adapting all the time, it's a never stopping, never stopping process. And that, that's what makes the whole thing go. The other thing about resilience is it's expensive. It requires continuous and energy and resource inputs. It's delicate and can be disrupted by loss of feedback. It's susceptible to disease and it's limited. It doesn't last forever. I don't know if you know this, but you're all going to die someday. And so re's a limitation there. There's a kind of a, a sell by date for this in, in this resilient system as there are in many. Okay. So that's, that's
so the first thing I'll point out is that bone has both a complex macro and micro architecture. On the left you see a picture of a section through a bone and you see the hard outer edge called compact bone. And then the inner bone, which is called cancellous bone, which is just kind of woven thing with all these spicules. If you expand that a bit, you'll look inside. You'll see that in fact there's a micro architecture here which has got these central things which are canals. You see them prominently displayed here with the circular cells, aligning them and creating this bony material. Bone itself is not living material. It is the bony, the strength part of bone stuff is hydroxyapatite crystals. They're inorganic
material, but they're laid down by organic processes. But there is this structure and architecture here, which is, it has a D is different at different scales but all integrates together.
new bonus laid down along stream lines. So it turns out that bone has sensors that allow the detection of mechanical strain and redirect the process of chewing up bone that is destroying old bone and laying down new bone so that the new bone is aligned along the lines of stream. This is a really important idea. Bone is expensive to make, hard to maintain, very demanding of resources and energy and you don't want it. It makes teleological sense not to use too much to do this. So we're very sparing in the way that we make bone and the regular strain that organisms experience leads to a regular pattern in the way that bonus laid down. If you look at the picture on the upper left, which is a slice through a femur, the head of the femur there you can see what looks like a little boxlike thing right at the tip of the head of the femur. And that box like structure, which looks like a little line going sort of that, that sort of marks the diameter of the sphere there, that line and that box that's inside there are present because of the patterns of strain that are caused by locomotion, by being upright. And it's common across all of us to have that pattern there. Even though it's not programmed anywhere in molecular biology, there's no, no gene that says make bone and lay it down in this particular pattern inside. It's the constant experience of strain that causes the bone to be restructured in that way so that it becomes powerful and supports those loads. by the way, there may be an optimal strain experience. This goes perhaps a metaphorically to the issues of burnout and things like that. You can have too much strain. You can accumulate fractures for example, faster than you can heal them. And so we see damages that come from high loading over time. The remodeling of bone, this constant process is going on in the background is actually fairly complicated. But the key thing is that it's locally directed but globally modulated and it produces the repair of microfractures that we're accumulating all the time. So the reason our signal skeletons are strong is not because bonus, so impervious to damage, but because small damages are constantly being repaired. This process of remodeling that's going on is identifying and fixing these small fractures all the time. And as a consequence, our experiences that bonus, solid and durable that process fits into the recycling of calcium and phosphorus as well because it turns out that the chewing up of bone that happens in the little cells you see here mostly at the left of the slide, which are called osteoclast, is done by secretion of hydrochloric acid, which dissolves the bone and then returns its mineral ions back into the circulation where it can be used for other purposes. Calcium is really crucial because all of our contractual activities, your heart, your muscles, and in fact the inside cell activities all depend upon calcium function. Calcium is by far the most tightly regulated ion in the body. And so having a big supply of calcium, which is in short a short supply world is actually very valuable. You have about a kilogram of calcium in your body and it's most 99% of it is stored in bone. The way calcium
homeostasis has maintained is via of complex thing that involves the kidney and the gut and absorption, vitamin D, parathyroid hormone and a variety of other things. But basically there's this very big complicated control network that is essentially regulating the level of calcium your body by taking calcium when it's in low, when it's low in the, in the body, low in circulation and, and taking it from bone by increasing the amount of osteoclastic activity and the return of calcium and depositing calcium when you have a surfeit of it into bone, creating it at that time. And this happens in small areas. It has, and it also has very large influences. The figure on the right is kind of a schematic of some of the signaling that goes on. And I'll just show you a list of some of the signals that are here. And this is just a partial list of some of the signals that are involved. And they have funny names because of the way the research is going on and not all entirely meaningful or, or easy to follow. But there's one here in particular I'd like you to pay attention to which is P T H R P, parathyroid, hormone related protein, which is one of the signals that is involved in this process of directing the the consumption and remodeling of bone. Okay. Deep science. Let's go to something a little bit more straight forward. Here is a radiograph. This is an X Ray taken of a 25 year old male who came to the emergency reporting that he had kicked a limp post in a fit of anger and later noticed he had quote, difficulty walking unquote. you, you might be able to, even those of you who are not medically trained may be able to see in this picture some evidence of the difficulty that was involved in. And although the report doesn't include anything explicit about this one suspects that alcohol was engaged here at some point. But what happens of course, is that you can sustain a fracture like this. And then the fracture gets repaired. How many of you have fractured a bone, substantial portion of the audience, at least half. And you will have noticed that when you fractured the bone, that there was a period of time when it was unstable. And then gradually it became that you felt a lump there underneath the surface. If you touched it, you could feel that it was swollen and lumpy and that over the next year or so, that lump went away. And that process is related to the resilience of bone and the methods of repair. And you see here on the left when you first break a bone, you have a - you injure the periostin, which is the cellular lining that covers the bone. And then you have a hematoma, which isessentiallya bruise in the bone. And this activity causes the influx of a whole bunch of different kinds of cells, notably cartridge cartilage cells, which then fill up the area and provide a kind of short termsort of connection between things. And then there's this invasion of the cartilage by these active elements that lay down bone and what of course they do over time as they lay down fairly thick amount of bone of what's called a callus and that's what you were feeling in the year after you broke that bone. That lump there is called the callus and it's bone. It's regular bone in the in the normal sense, but the process of remodeling which takes
years afterwards or months to years afterwards. That process of sin, stress and strain gradually sculpts that callus down until it is back to very much like what the bone was before that is detecting where the strain is, causes excess bone to be chewed up, new bonus laid down, but only in the areas where the strain is high and this remodeling process gradually restores the shape of the bone and you'll have noticed that your own callus gradually became less and less until you finally didn't notice it. That's the remodeling process that's going on all the time and it does take a long time, but it's a very important one because again, it restores these functions. Now this is something that's been going on for a very long time. It doesn't turn out very well. Here's a picture series of
pictures from aa, an Indian excavation from about 1400 a D these are the bones from a burial site of, an elderly at the time, 50 year old Indian woman who had broken her femur. And you can see the break here. It's pretty clear that there's one that's been badly damaged in the other that's not there appear. And quite noticeably there's the place where the break has occurred is a very large, thick clumpy thing. And you'll also notice that the new bone is the repaired bone is much shorter than the other one. This woman would have walked if she walked at all afterwards with a terrible limp because one leg was about an inch and a half shorter than the other. And the reason this happens is because the muscles that hold together across the length of the bone, when it's broken, pull the bones, the bone ends across each other so they're no longer aligned and shorten it up. And then of course the same healing process goes on and it heals in that awkward position. Why is this not a problem for us now? Well, in fact, now we understand this and we avoid that. We understand that bone repair mechanisms will knit broken pieces together, right? If you know that, if you're going to have a fracture, that the normal response to that will be to knit those pieces together. And the whole point of this is to then create a, an alignment before that happens by what's called reduction. That means reducing the fracture so that it just a now aligned and then keeping those, the position of those bones relatively stationary relative to each other so that the healing process will end up restoring that original fictional form. And as those of you who have broken something and had a cast, no mechanical stabilization is the key. You need to keep the mechanical alignment of bone in place for a long enough period of time that that will heal and be relatively strong and then you can take that cast or whatever's holding it together off.Yeah.
Uh,
a fairly substantial amount of effort has been put into this and trying to find
ways to, to provide this stabilization and reduction.
There's a thing called external fixation.
Some of you may have seen someone with an external fixator on.
This is not uncommonly used if the bone if the injury has broken the skin.
But you can also do what's called internal fixation or an open reduction and
internal fixation that w where you do a surgical procedure,
you see this in the middle where you cut through the skin,
you go down to the bone and then you do something to hold that bone together.
You might put a plate and some screws in,
or as you see in the picture on the far right you might do what's called an
intramedullary nail. This is a long spike.
It's about this long depending upon how big the person and it's a big long,
it looks like a nail. And then what happens is you
get the person in the right position, you reduce the fracture by putting traction on the leg, pull it apart like this. So that the ends of the bone are now in line and then you take a hammer and you'd drive the nail down through the hip from the top as you see all the way down and cross that and bridge that broken area and then you put a little pin in the top to hold it there so it doesn't slide out. You can see why I'm an anesthesiologist,
but in all these cases, the whole point of this is to to allow the natural healing processes to make the
bone and restore the bone position of function that it was in before. It's the issue is what is that position and what is the function? We don't heal these things. We are not. The orthopedic surgeons do not heal bone. What they do is they rearrange bone and hold it in place for a long enough period of time that the natural processes that are resilient in bone will lead to a desirable result. Okay. This is a pretty important idea. In fact, physicians in general are not healers, although they're often described that way. The body is the healer the physician creates, if they're lucky, a situation where the alignments and the functions are such that the healing can take place. But we depend upon that healing. And in fact, we know for instance, if you have deficiencies of nutrition or other diseases that the healing is, can be quite difficult. This idea about fixation is actually...and healing is actually rather old. Here's a picture on the left of some splints that were taken out of aa tomb in Egypt and reported by George Smith in 1908. And the British medical journal, these are the most ancient splints that anyone has found. You see some of the broken bones there and the splints were wrapped around this. And there's a thing called the Edwin Smith papyrus Iris from about 1600 BC, which you see here on the right. And this is a, the first medical text that we know about and a portion of this is devoted to taking care of broken bones. here, here's it. Here's the hieroglyphs written on the left. And and because I'm sure you're a little rusty and you're highly hieroglyphics. I've added the translation on the right. but here's what it says. This is for a broken bone of the arm and it says that it should just place him prostrate on his back with something folded between his two shoulder blades. Though it should have spread out with his two shoulders in order to stretch his upper arm until the break falls into place. That's the reduction we're talking about though should us make for him two splints of linen and that should us apply for him. One of them both on the inside of his arm and the other of them both on the underside of his arm though should us bind it with your move. This is the word for plaster of Paris, but Paris hadn't been invented yet
and treat it afterwards with honey every day till he recovers.
It's pretty good medical advice. And in fact there were a groups of people in ancient Egypt and ever since who are bone setters whose function it is to produce reduction and fixation and allow or bone to heal. So I would argue that this is a kind of resilience engineering that is, we understand the resilience of the system that we are dealing with and we are doing engineering. So that that resilience plays out the long avenues which are desirable, that that produce a desired result. The resilience isn't ours. We didn't create it. We're not the owners of it. We're not the generators of it, but we know that it's there. And interestingly enough and enough study you, you, you are able to get this kind of construction that, that will allow you to make use of that and heal in good function. So just to review, you know, the whole idea here is that that we are getting multiple functions for bone. It's a storehouse of calcium and other things. It plays a actually a number of different roles. it's a constantly undergoing replacement and there's this balance that exists, this dynamic balance between the destruction and construction and resilience engineering in this case is applying engineering to a resilient system that depends for its success on the presence of resilience. it requires of understanding how the resilience plays out. It can be successful even without understanding much about the mechanisms of resilience and it benefits from greater understanding of the sources and modulators of resilience. It was known fairly early, for instance, that nutrition is pretty important to bone healing.Well,
pretty good, huh?
Now the famous Thomas Hughes wrote in his book,
Tom Brown school holidays, school days. Life isn't all beer and Skittles.
bone is not perfect. There are a number of diseases of bone.
One's called osteogenesis imperfecta. This is a problem,
a inherited problem where bone doesn't make the right calcium and lay things
down.
There's a disease called Paget's disease where bonus actually absorbed too much.
There's osteoporosis.
Some of you may know this because you may have elderly parents or you may be
approaching old age yourself and you may note that that osteoporosis is a major
cause of morbidity. In the United States there are cancers of bone.
There's an osteosarcoma, which some of you have heard about.
There are problems associated with malnutrition. For instance, rickets,
you see this in bowed-leg children used to be very common in the United States,
not seen very much anymore. And then you can have disorders of the signaling,
hyperparathyroidism can,
which turns on the osteoclast and causes them to chew up bone can actually,
you can have a tumor of the parathyroid that seats secretes too much of this
stuff.
And out of control with the calcium regulation system causes the chewing up the
bone and the destruction of bone leads to fractures and kidney stones.
And so I want to take one example of this, which is osteoporosis.
It's a very important medical condition.
I don't want to call it a disease because it's probably a, a, a,
a natural consequence of aging, but it's,
it's more noticeable in older people and it's particularly got a preference for
women.
you see here a set of radiographs actually that are from CTS of a piece of a
vertebra and a normal person. And then with osteoporosis.
And the process here is,
is one that where the absorption of bone has become greater than the production
of bone.
And so you lose bone mass over time and it's,
it's actually quite difficult to, to counter that.
The goal would be to block the, absorb the resorption of
bone and, and sort of turn down, modulate down the osteoclastic activity or to increase the production of bone, turn up the osteoblastic activity in order to develop this sort of stuff.
many of you will recognize that the consequences of osteoporosis, typically hip or vertebral fractures in elderly women, women who are older, the typical person is a woman that age 60 or 70, now 70 or 80, who has a hip fracture or a vertebral fracture. These are really not so much a problem with the fracture per seas the fact that the bone has lost its strength because of this imbalance between creation and destruction. And there are two ways you can fix this. One is you can try and turn down that, that process that's chewing. And the other way is you can try and increase the osteoblastic activity that lays down bone. You'll remember that I talked to you earlier about the signaling business that goes on here and that I asked you to pay attention to one particular signal, which is parathyroid hormone related protein. P, T, H, R, P. And over the past five years, actually the research goes back about 15 or more years or perhaps even much longer. There's been a lot of interest in understanding the signaling, signaling processes and trying to use them. And there are now drugs notably abaloparatide and teriparatide, which are molecular signalers, which mimic PTHRP. There are molecularly developed things that are like parathyroid hormone replaced the protein and the presence of these at intervals, you have to do it, you have to produce the stimulus at intervals, generates a signal, which says basically turn up the osteoblastic activity that makes bone
and you give this stuff, it's an injection you give it once a week or twice a week to people who are at risk for it. And interestingly enough, abaloparatide significantly reduces the incidence of vertebral fractures compared with placebo, with a risk reduction of about 91%, which I will tell you in the medical world is the big deal, right? We don't get that kind of risk reduction very often. And so many people, especially those at risk for osteoporosis notably, interestingly enough uh,
white women, older of a European extraction and smokers especially we'll get this drug from their physicians. I want to point out that it's still not all Skittles and beer. There are, there are problems with these drugs in there and at least in rats, at very high doses, a continuous exposure to abaloparatide can produce some cancers. That is, you can turn on these mechanisms in ways that lead to terrible results. But this is a type of resilience engineering. I would, I would offer you this as a type of resilience engineering. It alters the underlying resilience mechanisms that are present in the system. It depends for its success on a really deep understanding of resilience. That is you have to actually understand and be able to manipulate the signaling by the way that drug has given in microgram amounts, right? So we're talking, you know, things were only a few molecules of this are actually reaching the cells. it, it tends to retard the loss of the adaptive capacity of bone. And it also, by the way, generates new types of hazard, which is something those of us interested in resilience engineering should probably think about because work on resilience engineering may not all be Skittles and beer. There may be some downside to this, which is related to our manipulation directly of these powerful mechanisms that involve signaling bone reminds us that resilience requires continuous energy and resources. The history of bone appears in its structure. You can tell what has happened to a person by looking at the structure of bone, which I think is a very interesting sort of thing. If you think at the organizational level of your own place, you can see the history of the organization and the architecture of its software. it has its own pathologies. It's vulnerable to a number of disruptions, and it turns out that bone is a lot easier to you. Bony resilience is a lot easier to use than it is to create this resilience engineering that I talked about. The first kind of resilience engineering, you can call it resilience engineering type one, if you like, but this first type of resilience engineering is engineering applied to a resilient system. It depends for its success on the presence of resilience in that system. It can be successful even without understanding very much about the mechanisms of resilience. It does benefit from greater understanding of the sources and modulators of resilience, and that's at least 3,500 years old. We've been doing resilience engineering for 3,500 years. There's other kinds of resilience engineering, the one where people are using the modulation of the signaling in microgram amounts to alter the balance. That dynamic balance between destruction and creation. That leads to a more or less static looking picture of your skeleton is only about five years old. It is a direct, it is an attempt to directly alter the resilience of the living system. It's therefore got some hazards attached to it, but also some great possibilities, particularly the fact that micrograms can be used to influence. This tells you how powerful it is. It depends critically on the success of for its success on deep understanding of resilience. You wouldn't 3,500 years ago, 2000 years ago, a thousand years ago, even even 60 or 70 years ago, this would have been inconceivable. No one could possibly have imagined doing this. This is the result of many, many hundreds of years of intense effort to try and understand these mechanisms and many, many new techniques that have been brought to bear only in the past couple of decades. It does generate new types of hazard, but it's particularly interesting to me because it's, it is a different, it's qualitatively a different kind of resilience engineering that is, I'm trying to engineer the resilience rather than you do engineering that exploits the resilience. And I think we often confuse these two or talk about these two as though they were one. And I think interestingly enough, many in people who are interested in resilience initially are interested in trying to enhance resilience or build up resilience or make resilience stronger or find new ways to generate resilience. And a whole bunch of other sorts of descriptive terms, which is that resilience engineering that's on the right hand side, right? It's the modulation directly of resilience. But if we look at it a bit more closely, we would see in the history of your own domain and many others, the presence of resilience engineering over a much longer period of time. That is people understanding resilience is present in your system and finding ways to make use of that resilience to engineer the ways in which that resilience is brought to bear. And so I would give you PagerDuty and Rundeck and all the other sponsors of this conference as examples of resilience engineering, their attempts to bring the resilience, which is located in the people who are actually maintaining your systems to bear in ways that allow it to flow more effectively to restore that function. And I think we give that to perhaps some short shrift in, we're so fascinated by the idea of resilience and creating resilience that we immediately want to do this thing over here. Not recognizing that to do that requires quite a deep understanding of the sources and operational characteristics of resilience. And that's quite a big undertaking. But I would suggest to you that you are doing resilience engineering in your work on a daily basis. It may not get that label or a title, but just what you are doing every day and, and like the orthopedics surgeons, you understand enough about the resilience in the system to be able to engineer it such that the resilience will play out in ways that are productive and functional. You understand that you have to modulate that by providing the various sorts of nutrition and raw resources and other things. You understand that those are, are essential for that resilience to play out and enumerating and understanding those things, which has been the tradition in orthopedic and orthopedics for at least a 3,500 years is crucial to making progress. There is the possibility of doing this kind of resilience engineering the type two or, or the other kind, the direct manipulation of resilience. But I think it's going to prove to be much more difficult for us because we will have to have a really intimate understanding of what resilience is and how it works in these systems in order to be able to do this very effectively.
Well, as my psychiatrist friends see, I see we're coming close to the end of our time together.
So why is this important? I think you are the people who are most likely to be in a position to recognize
and perhaps to not control, but let's say modulate the way resilience is used and engineered
the engineering around resilience to achieve particular ends. I think you're also quite sensitive to the ways in which resilience is vulnerable, the kinds of diseases, the collection, just like Paget's disease and osteosarcoma and all those that we saw on bone there. There are pathologies in your organizations as well that will tend to Rob your skeleton of the resilience. And there are also uh, processes in the background, which are, which are involve continuous renewal such that we don't really see them, we view them as static. The new people coming to your organization to learn about systems, the old ones leaving, the restructuring of architectures, the call, rotors, all of those things are a kind of background process of, of destruction and renewal that creates a kind of dynamic balance that preserves resilience and makes it available for dealing with the kinds of problems that you're going to encounter. It's for this reason that I commend to you the idea of bone as a model for not as a model, as an archetype for resilience. And I hope that when people say to you in the future, what, what is this resilience thing? What, tell me what resilience is. What does resilience mean? Or can you give me an example of resilience or resilience engineering that the first example that will come to mind for you is bone. So I think it's really beautiful. I think it's, it's got a quality to it that is, almost,
dare I say spiritual. that, that has so many of the aspects of resilience built into this one nice example, that exploring it and understanding it is likely to prove to be very valuable for you in the future. Thank you very much for your kind attention.
most of you are dealing with complexity in some form or other and trying to struggle with, with the consequences of that. And I'm going to talk about an area that exhibits all of these properties, but that is not your home base. I'm going to talk about bone and I think in the end that you will, my hope is that you will come to believe that bone is not a model of resilience or a metaphor for resilience, but the archetype of what resilience is that when we try to understand resilience, the first thing that should come to mind would be bone. And if I succeed today for you in the future when someone says, what is resilience, the example that you will give to them as bone. I'm also going to have to talk a little bit about resilience engineering because the engineering part of resilience engineering is, is a pretty complicated sort of idea and much more difficult to pin down than just resilience itself. Okay. We'll just do those two things. That's it. Nothing big. And because my kids are all in advertising and they're constantly telling me to cut to the chase in conclusion, let me say this
the, the, the bottom line here is pretty straight forward at least about bone and resilience and how it works. bonus continuously remodeled. Many of you probably are not aware of this, but your skeleton is replaced about every 10 years. And that's pretty remarkable because from your perspective, the skeleton is a kind of static thing. It's always there. You have it. And as long as you don't do too many bad things to it, it doesn't change very much. But in fact, your skeleton is constantly being replaced. The making of new bone is in a dynamic balance with the destroying of old bone. And this is a process that's energy requiring and takes place all the time. And because it's happening at this little level, you don't notice it. But if I were going to pick one thing to remember from this talk, it is the idea of this dynamic balance between creation and destruction, which then provides the platform for all the resilience that we see. Resilience is constantly present, it's constantly enacted, it's constantly requiring energy and we are unaware of that because most of the time it's happening in the background and at a fairly little level so that we don't see it playing out. The other thing is that the demolition and construction of bone is directed by mechanical strain. And this is really important because resilience is focused on particular kinds of things in via via various sorts of mechanisms to achieve a specific ends. We'll talk a little bit about repair of some additional mechanisms. I don't want to talk about that in detail. Um, bone. But the other thing is that the system of bone is not just a skeletal system in the sense that it holds us up. It also provides other functions. It's the primary store in our body for calcium and phosphorous, which are both very important minerals and very, very difficult to get from the environment. And important to have. And it turns out that calcium is the most important ion in the body. finally, this idea about resilience is that it's all about signaling. There is no master controller and resilience. There's no high God of resilience, which directs everything and organizes it. In fact, it's a messy layered network that is actually performing these functions and we'll show you a little bit of the network even though it's not yet well understood and there's lots and lots of crosstalk in this network and a lot of cell level integration of the activities that are going on. Cells respond in a way that makes this all possible. bones resilience is what I would call Woodsian. And this is after Dave Woods. Dave Woods has, if you haven't looked at it, you certainly should. The four concepts for resilience and the implications for the future of resilience engineering and reliability engineering and system safety. But basically he's got four different ideas about what resilience is and the last two are the most important. One is this idea of graceful extensibility, that the system has, not a sharp boundary, but a rather soft boundary that that allows extension of its function. And the other is sustained adaptability. The idea that we are constantly adapting all the time, it's a never stopping, never stopping process. And that, that's what makes the whole thing go. The other thing about resilience is it's expensive. It requires continuous and energy and resource inputs. It's delicate and can be disrupted by loss of feedback. It's susceptible to disease and it's limited. It doesn't last forever. I don't know if you know this, but you're all going to die someday. And so re's a limitation there. There's a kind of a, a sell by date for this in, in this resilient system as there are in many. Okay. So that's, that's
so the first thing I'll point out is that bone has both a complex macro and micro architecture. On the left you see a picture of a section through a bone and you see the hard outer edge called compact bone. And then the inner bone, which is called cancellous bone, which is just kind of woven thing with all these spicules. If you expand that a bit, you'll look inside. You'll see that in fact there's a micro architecture here which has got these central things which are canals. You see them prominently displayed here with the circular cells, aligning them and creating this bony material. Bone itself is not living material. It is the bony, the strength part of bone stuff is hydroxyapatite crystals. They're inorganic
material, but they're laid down by organic processes. But there is this structure and architecture here, which is, it has a D is different at different scales but all integrates together.
new bonus laid down along stream lines. So it turns out that bone has sensors that allow the detection of mechanical strain and redirect the process of chewing up bone that is destroying old bone and laying down new bone so that the new bone is aligned along the lines of stream. This is a really important idea. Bone is expensive to make, hard to maintain, very demanding of resources and energy and you don't want it. It makes teleological sense not to use too much to do this. So we're very sparing in the way that we make bone and the regular strain that organisms experience leads to a regular pattern in the way that bonus laid down. If you look at the picture on the upper left, which is a slice through a femur, the head of the femur there you can see what looks like a little boxlike thing right at the tip of the head of the femur. And that box like structure, which looks like a little line going sort of that, that sort of marks the diameter of the sphere there, that line and that box that's inside there are present because of the patterns of strain that are caused by locomotion, by being upright. And it's common across all of us to have that pattern there. Even though it's not programmed anywhere in molecular biology, there's no, no gene that says make bone and lay it down in this particular pattern inside. It's the constant experience of strain that causes the bone to be restructured in that way so that it becomes powerful and supports those loads. by the way, there may be an optimal strain experience. This goes perhaps a metaphorically to the issues of burnout and things like that. You can have too much strain. You can accumulate fractures for example, faster than you can heal them. And so we see damages that come from high loading over time. The remodeling of bone, this constant process is going on in the background is actually fairly complicated. But the key thing is that it's locally directed but globally modulated and it produces the repair of microfractures that we're accumulating all the time. So the reason our signal skeletons are strong is not because bonus, so impervious to damage, but because small damages are constantly being repaired. This process of remodeling that's going on is identifying and fixing these small fractures all the time. And as a consequence, our experiences that bonus, solid and durable that process fits into the recycling of calcium and phosphorus as well because it turns out that the chewing up of bone that happens in the little cells you see here mostly at the left of the slide, which are called osteoclast, is done by secretion of hydrochloric acid, which dissolves the bone and then returns its mineral ions back into the circulation where it can be used for other purposes. Calcium is really crucial because all of our contractual activities, your heart, your muscles, and in fact the inside cell activities all depend upon calcium function. Calcium is by far the most tightly regulated ion in the body. And so having a big supply of calcium, which is in short a short supply world is actually very valuable. You have about a kilogram of calcium in your body and it's most 99% of it is stored in bone. The way calcium
homeostasis has maintained is via of complex thing that involves the kidney and the gut and absorption, vitamin D, parathyroid hormone and a variety of other things. But basically there's this very big complicated control network that is essentially regulating the level of calcium your body by taking calcium when it's in low, when it's low in the, in the body, low in circulation and, and taking it from bone by increasing the amount of osteoclastic activity and the return of calcium and depositing calcium when you have a surfeit of it into bone, creating it at that time. And this happens in small areas. It has, and it also has very large influences. The figure on the right is kind of a schematic of some of the signaling that goes on. And I'll just show you a list of some of the signals that are here. And this is just a partial list of some of the signals that are involved. And they have funny names because of the way the research is going on and not all entirely meaningful or, or easy to follow. But there's one here in particular I'd like you to pay attention to which is P T H R P, parathyroid, hormone related protein, which is one of the signals that is involved in this process of directing the the consumption and remodeling of bone. Okay. Deep science. Let's go to something a little bit more straight forward. Here is a radiograph. This is an X Ray taken of a 25 year old male who came to the emergency reporting that he had kicked a limp post in a fit of anger and later noticed he had quote, difficulty walking unquote. you, you might be able to, even those of you who are not medically trained may be able to see in this picture some evidence of the difficulty that was involved in. And although the report doesn't include anything explicit about this one suspects that alcohol was engaged here at some point. But what happens of course, is that you can sustain a fracture like this. And then the fracture gets repaired. How many of you have fractured a bone, substantial portion of the audience, at least half. And you will have noticed that when you fractured the bone, that there was a period of time when it was unstable. And then gradually it became that you felt a lump there underneath the surface. If you touched it, you could feel that it was swollen and lumpy and that over the next year or so, that lump went away. And that process is related to the resilience of bone and the methods of repair. And you see here on the left when you first break a bone, you have a - you injure the periostin, which is the cellular lining that covers the bone. And then you have a hematoma, which isessentiallya bruise in the bone. And this activity causes the influx of a whole bunch of different kinds of cells, notably cartridge cartilage cells, which then fill up the area and provide a kind of short termsort of connection between things. And then there's this invasion of the cartilage by these active elements that lay down bone and what of course they do over time as they lay down fairly thick amount of bone of what's called a callus and that's what you were feeling in the year after you broke that bone. That lump there is called the callus and it's bone. It's regular bone in the in the normal sense, but the process of remodeling which takes
years afterwards or months to years afterwards. That process of sin, stress and strain gradually sculpts that callus down until it is back to very much like what the bone was before that is detecting where the strain is, causes excess bone to be chewed up, new bonus laid down, but only in the areas where the strain is high and this remodeling process gradually restores the shape of the bone and you'll have noticed that your own callus gradually became less and less until you finally didn't notice it. That's the remodeling process that's going on all the time and it does take a long time, but it's a very important one because again, it restores these functions. Now this is something that's been going on for a very long time. It doesn't turn out very well. Here's a picture series of
pictures from aa, an Indian excavation from about 1400 a D these are the bones from a burial site of, an elderly at the time, 50 year old Indian woman who had broken her femur. And you can see the break here. It's pretty clear that there's one that's been badly damaged in the other that's not there appear. And quite noticeably there's the place where the break has occurred is a very large, thick clumpy thing. And you'll also notice that the new bone is the repaired bone is much shorter than the other one. This woman would have walked if she walked at all afterwards with a terrible limp because one leg was about an inch and a half shorter than the other. And the reason this happens is because the muscles that hold together across the length of the bone, when it's broken, pull the bones, the bone ends across each other so they're no longer aligned and shorten it up. And then of course the same healing process goes on and it heals in that awkward position. Why is this not a problem for us now? Well, in fact, now we understand this and we avoid that. We understand that bone repair mechanisms will knit broken pieces together, right? If you know that, if you're going to have a fracture, that the normal response to that will be to knit those pieces together. And the whole point of this is to then create a, an alignment before that happens by what's called reduction. That means reducing the fracture so that it just a now aligned and then keeping those, the position of those bones relatively stationary relative to each other so that the healing process will end up restoring that original fictional form. And as those of you who have broken something and had a cast, no mechanical stabilization is the key. You need to keep the mechanical alignment of bone in place for a long enough period of time that that will heal and be relatively strong and then you can take that cast or whatever's holding it together off.
get the person in the right position, you reduce the fracture by putting traction on the leg, pull it apart like this. So that the ends of the bone are now in line and then you take a hammer and you'd drive the nail down through the hip from the top as you see all the way down and cross that and bridge that broken area and then you put a little pin in the top to hold it there so it doesn't slide out. You can see why I'm an anesthesiologist,
but in all these cases, the whole point of this is to to allow the natural healing processes to make the
bone and restore the bone position of function that it was in before. It's the issue is what is that position and what is the function? We don't heal these things. We are not. The orthopedic surgeons do not heal bone. What they do is they rearrange bone and hold it in place for a long enough period of time that the natural processes that are resilient in bone will lead to a desirable result. Okay. This is a pretty important idea. In fact, physicians in general are not healers, although they're often described that way. The body is the healer the physician creates, if they're lucky, a situation where the alignments and the functions are such that the healing can take place. But we depend upon that healing. And in fact, we know for instance, if you have deficiencies of nutrition or other diseases that the healing is, can be quite difficult. This idea about fixation is actually...and healing is actually rather old. Here's a picture on the left of some splints that were taken out of aa tomb in Egypt and reported by George Smith in 1908. And the British medical journal, these are the most ancient splints that anyone has found. You see some of the broken bones there and the splints were wrapped around this. And there's a thing called the Edwin Smith papyrus Iris from about 1600 BC, which you see here on the right. And this is a, the first medical text that we know about and a portion of this is devoted to taking care of broken bones. here, here's it. Here's the hieroglyphs written on the left. And and because I'm sure you're a little rusty and you're highly hieroglyphics. I've added the translation on the right. but here's what it says. This is for a broken bone of the arm and it says that it should just place him prostrate on his back with something folded between his two shoulder blades. Though it should have spread out with his two shoulders in order to stretch his upper arm until the break falls into place. That's the reduction we're talking about though should us make for him two splints of linen and that should us apply for him. One of them both on the inside of his arm and the other of them both on the underside of his arm though should us bind it with your move. This is the word for plaster of Paris, but Paris hadn't been invented yet
and treat it afterwards with honey every day till he recovers.
It's pretty good medical advice. And in fact there were a groups of people in ancient Egypt and ever since who are bone setters whose function it is to produce reduction and fixation and allow or bone to heal. So I would argue that this is a kind of resilience engineering that is, we understand the resilience of the system that we are dealing with and we are doing engineering. So that that resilience plays out the long avenues which are desirable, that that produce a desired result. The resilience isn't ours. We didn't create it. We're not the owners of it. We're not the generators of it, but we know that it's there. And interestingly enough and enough study you, you, you are able to get this kind of construction that, that will allow you to make use of that and heal in good function. So just to review, you know, the whole idea here is that that we are getting multiple functions for bone. It's a storehouse of calcium and other things. It plays a actually a number of different roles. it's a constantly undergoing replacement and there's this balance that exists, this dynamic balance between the destruction and construction and resilience engineering in this case is applying engineering to a resilient system that depends for its success on the presence of resilience. it requires of understanding how the resilience plays out. It can be successful even without understanding much about the mechanisms of resilience and it benefits from greater understanding of the sources and modulators of resilience. It was known fairly early, for instance, that nutrition is pretty important to bone healing.
bone and, and sort of turn down, modulate down the osteoclastic activity or to increase the production of bone, turn up the osteoblastic activity in order to develop this sort of stuff.
many of you will recognize that the consequences of osteoporosis, typically hip or vertebral fractures in elderly women, women who are older, the typical person is a woman that age 60 or 70, now 70 or 80, who has a hip fracture or a vertebral fracture. These are really not so much a problem with the fracture per seas the fact that the bone has lost its strength because of this imbalance between creation and destruction. And there are two ways you can fix this. One is you can try and turn down that, that process that's chewing. And the other way is you can try and increase the osteoblastic activity that lays down bone. You'll remember that I talked to you earlier about the signaling business that goes on here and that I asked you to pay attention to one particular signal, which is parathyroid hormone related protein. P, T, H, R, P. And over the past five years, actually the research goes back about 15 or more years or perhaps even much longer. There's been a lot of interest in understanding the signaling, signaling processes and trying to use them. And there are now drugs notably abaloparatide and teriparatide, which are molecular signalers, which mimic PTHRP. There are molecularly developed things that are like parathyroid hormone replaced the protein and the presence of these at intervals, you have to do it, you have to produce the stimulus at intervals, generates a signal, which says basically turn up the osteoblastic activity that makes bone
and you give this stuff, it's an injection you give it once a week or twice a week to people who are at risk for it. And interestingly enough, abaloparatide significantly reduces the incidence of vertebral fractures compared with placebo, with a risk reduction of about 91%, which I will tell you in the medical world is the big deal, right? We don't get that kind of risk reduction very often. And so many people, especially those at risk for osteoporosis notably, interestingly enough uh,
white women, older of a European extraction and smokers especially we'll get this drug from their physicians. I want to point out that it's still not all Skittles and beer. There are, there are problems with these drugs in there and at least in rats, at very high doses, a continuous exposure to abaloparatide can produce some cancers. That is, you can turn on these mechanisms in ways that lead to terrible results. But this is a type of resilience engineering. I would, I would offer you this as a type of resilience engineering. It alters the underlying resilience mechanisms that are present in the system. It depends for its success on a really deep understanding of resilience. That is you have to actually understand and be able to manipulate the signaling by the way that drug has given in microgram amounts, right? So we're talking, you know, things were only a few molecules of this are actually reaching the cells. it, it tends to retard the loss of the adaptive capacity of bone. And it also, by the way, generates new types of hazard, which is something those of us interested in resilience engineering should probably think about because work on resilience engineering may not all be Skittles and beer. There may be some downside to this, which is related to our manipulation directly of these powerful mechanisms that involve signaling bone reminds us that resilience requires continuous energy and resources. The history of bone appears in its structure. You can tell what has happened to a person by looking at the structure of bone, which I think is a very interesting sort of thing. If you think at the organizational level of your own place, you can see the history of the organization and the architecture of its software. it has its own pathologies. It's vulnerable to a number of disruptions, and it turns out that bone is a lot easier to you. Bony resilience is a lot easier to use than it is to create this resilience engineering that I talked about. The first kind of resilience engineering, you can call it resilience engineering type one, if you like, but this first type of resilience engineering is engineering applied to a resilient system. It depends for its success on the presence of resilience in that system. It can be successful even without understanding very much about the mechanisms of resilience. It does benefit from greater understanding of the sources and modulators of resilience, and that's at least 3,500 years old. We've been doing resilience engineering for 3,500 years. There's other kinds of resilience engineering, the one where people are using the modulation of the signaling in microgram amounts to alter the balance. That dynamic balance between destruction and creation. That leads to a more or less static looking picture of your skeleton is only about five years old. It is a direct, it is an attempt to directly alter the resilience of the living system. It's therefore got some hazards attached to it, but also some great possibilities, particularly the fact that micrograms can be used to influence. This tells you how powerful it is. It depends critically on the success of for its success on deep understanding of resilience. You wouldn't 3,500 years ago, 2000 years ago, a thousand years ago, even even 60 or 70 years ago, this would have been inconceivable. No one could possibly have imagined doing this. This is the result of many, many hundreds of years of intense effort to try and understand these mechanisms and many, many new techniques that have been brought to bear only in the past couple of decades. It does generate new types of hazard, but it's particularly interesting to me because it's, it is a different, it's qualitatively a different kind of resilience engineering that is, I'm trying to engineer the resilience rather than you do engineering that exploits the resilience. And I think we often confuse these two or talk about these two as though they were one. And I think interestingly enough, many in people who are interested in resilience initially are interested in trying to enhance resilience or build up resilience or make resilience stronger or find new ways to generate resilience. And a whole bunch of other sorts of descriptive terms, which is that resilience engineering that's on the right hand side, right? It's the modulation directly of resilience. But if we look at it a bit more closely, we would see in the history of your own domain and many others, the presence of resilience engineering over a much longer period of time. That is people understanding resilience is present in your system and finding ways to make use of that resilience to engineer the ways in which that resilience is brought to bear. And so I would give you PagerDuty and Rundeck and all the other sponsors of this conference as examples of resilience engineering, their attempts to bring the resilience, which is located in the people who are actually maintaining your systems to bear in ways that allow it to flow more effectively to restore that function. And I think we give that to perhaps some short shrift in, we're so fascinated by the idea of resilience and creating resilience that we immediately want to do this thing over here. Not recognizing that to do that requires quite a deep understanding of the sources and operational characteristics of resilience. And that's quite a big undertaking. But I would suggest to you that you are doing resilience engineering in your work on a daily basis. It may not get that label or a title, but just what you are doing every day and, and like the orthopedics surgeons, you understand enough about the resilience in the system to be able to engineer it such that the resilience will play out in ways that are productive and functional. You understand that you have to modulate that by providing the various sorts of nutrition and raw resources and other things. You understand that those are, are essential for that resilience to play out and enumerating and understanding those things, which has been the tradition in orthopedic and orthopedics for at least a 3,500 years is crucial to making progress. There is the possibility of doing this kind of resilience engineering the type two or, or the other kind, the direct manipulation of resilience. But I think it's going to prove to be much more difficult for us because we will have to have a really intimate understanding of what resilience is and how it works in these systems in order to be able to do this very effectively.
Well, as my psychiatrist friends see, I see we're coming close to the end of our time together.
So why is this important? I think you are the people who are most likely to be in a position to recognize
and perhaps to not control, but let's say modulate the way resilience is used and engineered
the engineering around resilience to achieve particular ends. I think you're also quite sensitive to the ways in which resilience is vulnerable, the kinds of diseases, the collection, just like Paget's disease and osteosarcoma and all those that we saw on bone there. There are pathologies in your organizations as well that will tend to Rob your skeleton of the resilience. And there are also uh, processes in the background, which are, which are involve continuous renewal such that we don't really see them, we view them as static. The new people coming to your organization to learn about systems, the old ones leaving, the restructuring of architectures, the call, rotors, all of those things are a kind of background process of, of destruction and renewal that creates a kind of dynamic balance that preserves resilience and makes it available for dealing with the kinds of problems that you're going to encounter. It's for this reason that I commend to you the idea of bone as a model for not as a model, as an archetype for resilience. And I hope that when people say to you in the future, what, what is this resilience thing? What, tell me what resilience is. What does resilience mean? Or can you give me an example of resilience or resilience engineering that the first example that will come to mind for you is bone. So I think it's really beautiful. I think it's, it's got a quality to it that is, almost,
dare I say spiritual. that, that has so many of the aspects of resilience built into this one nice example, that exploring it and understanding it is likely to prove to be very valuable for you in the future. Thank you very much for your kind attention.