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Authors: E. Paul Zehr

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Integrity of Implants in Iron Man

Please think back to the revision of the origin story I suggested for Tony (have a peek back at
chapter 7
). Along with this revision is the corresponding implication that the use of the implantable cardioverting defibrillator (ICD) has for his activity as Iron Man. One of the controversies around ICDs, though, is how active people should be if they have an implantation. Typically, aggressive contact sports or vigorous exercise are not recommended for those with ICDs. There is concern over how well they would function in such cases and concern over inappropriate shocks occurring. That means that the function of the defibrillator itself could interrupt normal heart rhythm during extreme activity and lead to more significant problems. So, the upshot of all of this is that Tony Stark would likely have a difficult and dangerous time being Iron Man. He is clearly subjected to very vigorous exercise and extreme contact—for example getting smashed around by Iron Monger as in the first
Iron Man
movie. This would definitely lead to the possibility of inappropriate shocks, or, more importantly, increased breakdown of the electrical leads used to provide the shocks for restoring heart rate.

Normally, there can be a steady increase in failure rate and problems eight to ten years after implantation of a cardioverting defibrillator. This means the best case is that Tony may well need another implant after about a decade. However, his work as Iron Man clearly isn't the “best case” for long-term stability and integrity of the ICD. How much it would be shortened is almost impossible to determine, because the data aren't really available on how the kind of violent activity that Iron Man experiences may affect the lifespan of ICDs. However, there is some research on the need to replace cochlear implants for hearing restoration. After an implantation of a cochlear implant, current technology only sees a 5% chance of needing a replacement (called “revision” or “reimplantation”), which seems pretty good. Of interest and very relevant for what we have just been talking about, is that almost half of the cases where hardware failure has led to a revision surgery have involved a history of head trauma! So, all the bashing around we were just talking about clearly is quite hard on brain-machine interface.

Another consideration is the integrity of the nervous system and the electrode connection that would be necessary for the full integration of the suit needed for realistic use. It should be remembered that
it is very difficult to interface technology with biology. Based on state-of-the-art experiments with different animals, it seems only about 50% of implanted electrodes can be usefully employed. Of those that could be used, there is a significant reduction in “usefulness” over time. This is largely due to a process known as encapsulation or “reactive gliosis”—a type of scarring of the nervous system—associated with immune rejection. Think of the medical intervention needed to keep the body from rejecting a transplanted organ. Now imagine that instead of an organ a piece of machinery has been implanted into the brain.

Jennie Leach and colleagues describe the view that the bodily response to an implanted neuroprosthetic interface has a rapid acute response, characterized by injury, inflammation, and what is known as “microglial activation.” Nerve cells are neurons and other stuff. In the other stuff category we find glial cells. Microglia make up about 20% of glial cells in the brain and provide the main protective immune response cells in the brain and spinal cord. They are a kind of “macrophage,” which means they attack and digest invaders and foreign objects in the nervous system and are the first and main form of active immune response in the brain and spinal cord.

The immune response is typically to digest an intruder and, if it cannot be digested, to cover it up so that it can do no harm. Implanted electrodes cannot be easily destroyed so the cover-up process is instead the main outcome. This begins in the acute phase and continues in a chronic response, which results in the formation of a virtually impenetrable glial or fibrotic scar around the implant. An example of this cascade of events is shown in
figure 9.4
. Panel A shows the implantation of an electrode array (“Utah array”) inserted through the brain and implanted on the surface of the brain. The drawings in panels B through D are close-ups of the region right beside the implant (shown as dashed rectangle in A). Cellular organization in the cortex is shown prior to implantation (panel B), immediately after implant (“acute,” panel C), and in chronic implantation (panel D). The key point is that there is steadily increasing scarring of support neurons (glia), shown at the far left near the implant surface, and some death of neurons, largely related to inflammatory responses.

This cascade is also of concern for other kinds of neuroprostheses like retinal implants for vision and cochlear implants for hearing. An interesting approach to deal with the significant scarring problem for cochlear implants has been to use pharmacological treatments to help trick the nervous system. One such treatment that has shown some promise is to use brain-derived neurotrophic factor (BDNF), which is a major player in a family of chemicals that help in neural development and neural plasticity. In order to avoid the problem of scarring, tissue engineers and nanotechnology experts are working on ways to make the implant appear more biological to the body using means such as this. Even though this pharmacological approach has promise, there is a long way to go to get to a stable enduring implant like that needed for a full brain-machine interface in an Iron Man suit. And then, on top of that, to have the brain subjected to the kind of continual trauma that Tony would experience isn't really a recipe for long-term success.

Figure 9.4. An example of the cascade of events occurring in the brain after implantation of an electrode array for brain-machine interface. The implantation of an electrode array, known as a Utah array, on the surface of the brain (
A
). Close-ups of the region right beside the implant (
B
–
D
; shown as dashed rectangle in
A
). Cellular organization in the cortex is shown prior to implantation (
B
), immediately after implant (“acute,”
C
), and in chronic implantation (
D
). Note steadily increasing scarring of support neurons (glia), shown at the far left near the implant surface, and some death of neurons, largely related to inflammatory responses. Courtesy Leach (2010).

Training Keeps Tony's Brain from Getting Rusty

A big part of thinking about Iron Man's career is his ability to work against the normal decline of nervous system function that happens with aging. Maybe there is some protection from changes in the aging nervous system due to all his training? Biological aging—senescence—is a steady and inevitable process. Senescence captures the reduction in function that starts just around the third decade in humans. Good examples of aging-related changes in the nervous system are those in the motor system. As part of the motor unit concept we talked about earlier, recall that motor neurons in the spinal cord send out their axons to connect with the fibers in your muscles. Well, with aging motor neurons die. Since the motor neurons are the final relays for sending the commands to make muscle contract, it is reasonable to think that muscle strength would decline.

Between the ages of 20 to 90 years, half of the skeletal muscle mass can be lost and this causes a corresponding reduction in muscle strength. Muscle fibers also will die and in particular those in the fastest contracting motor units, the type IIa group. Despite all that going on, you wouldn't notice the reduction in motor neuron number and muscle fibers that much, because your nervous system has a great ability to cover up problems. Plasticity in the nervous system compensates for the death of muscle fibers and motor neurons in senescence in a very clever way. A large muscle in your leg could have 250 motor units in it, and each unit might connect to a thousand muscle fibers. The distribution is called the “innervation ratio,” and,
in this example, would be 1,000. By the time Tony Stark hits age 70, the number of his motor units might drop from 250 to 125 in this muscle. So, he would have lost 125 motor neurons. However, many of his muscle fibers (previously connected to those now-dead motor neurons) would remain alive. They would sit in his muscle waiting to do their normal jobs, and this would happen when other motor neurons innervating muscle fibers in that leg muscle send branches from their axons over to the muscle fibers that are now “disconnected” from their original neurons. This process is called “sprouting” and is similar to the process of sensory reinnervation we talked about earlier with the face transplantation. Overall, this process of sprouting creates much larger innervation ratios—in this example let's say it is now 1,500 fibers per neuron—and helps maintain strength as you age. This is very similar to what occurs in recovery from some nerve injuries and is affected by how much activity the nervous system sees. So, if Tony is very physically active, his ability to maintain the integrity of his motor system in this way will be improved.

We can extend the example of Tony's motor system to many other parts of his nervous system. The nervous system is just like all other systems and parts of your body. When not used repeatedly, your physiological systems try to be as efficient as they can be. The nervous system responds to stresses to minimize the effect. You have experienced this throughout your life probably without really paying much attention to it. If you have ever done some strength training, you have a good specific example in mind. Imagine doing a bunch of arm flexion exercises (“biceps curls”). The stress on the muscles doing those curls leads to an increase in strength. Now imagine you did a bunch of training and got stronger but then couldn't train for a while because you broke your arm (sorry—it is just an example. Nothing personal). Suddenly you wouldn't be able to use your one arm very much and it would get weaker. You removed the stress now, so your body doesn't maintain the muscle to the same level. However, because of your training, you had built up a bit of a reserve of muscle strength. You still did weaken when you weren't able to use your arm, but, the really important part is that you would still finish stronger than if you hadn't done the training in the first place. So, the training created a kind of reserve that helped buffer the lack of use that occurred later.

Well, you don't actually curl weights with your brain. But the command to do the curling comes from your brain. Tony Stark is
stimulating his brain by straining and training every time he does physical activity or interfaces with his Iron Man suit. He places a lot of extreme demands on his nervous system and creates a kind of “brain reserve” by doing this. Exercise can also stimulate the brain to not only maintain the neurons and synaptic connections but also to create new neurons. Since declining function in the nervous system is inevitable as Tony gets older (and which was really well described in the graphic novel
The End
from 2010), any reserve he can add will keep a higher function as he gets older.

Brain reserve describes the idea that larger brains with more neurons and more synaptic contacts might be better at dealing with problems during aging, for example, dementia and disorders like Alzheimer's disease. Cognitive reserve is specific to how brain reserve can affect the ability to think and reason when there is pathological damage to the brain. So, the more reserve you have means the less you will be affected by declines in function. This doesn't mean Tony Stark could stop the normal inherent decline in function. However, it does mean that he can reduce the impact of the decline. That old phrase of “use it or lose it” applies really well to all aspects of your nervous system!

How Long Will the Iron Avenger Last?

Let's assume that Tony avoids concussion (or at least too many of them), the bodily rejection of his brain-machine interface, and serious injury from falls and weapons blasts. Let's also assume that his heart remains healthy and that he keeps his mind in shape to be able to multitask efficiently. What then? When should he fly off to the retirement home for heroes?

In his origin story, we learn that Tony took control of Stark Industries at the age of 21 and that shortly after that had his little “incident” with some shrapnel that put him on the road to inventing Iron Man. Remember that Tony will take more than ten years to go through pilot and hand-to-hand combat training. Remember too that it took Rossy, Nuytten, and Sankai decades to modify their suits and that we allowed 40 years for Tony to go through that process.

If my math is correct, Tony will be in his 60s by the time he masters being Iron Man. Those of you who read
Becoming Batman
will recall that, using sports icons as a guide, we determined that Batman
would have to hang up his cape in his mid-50s, at the absolute latest. So at some point Tony may want to start inventing suits for younger crime fighters to wear. A big caveat, though, is that the estimates for all these timelines are based on thinking of pretty linear and steady progress towards the ultimate objective of Iron Man. But advances in science and engineering don't always work like that. There can be wholesale paradigm shifts (like those Thomas Kuhn talked about earlier) and suddenly fields can move forward in big jumps. For Tony Stark's sake (and for our own imaginations), let's assume some of those come along during his years of Iron Man research and development. I feel better thinking of Tony as both inventor and user—however short that career as user might be.

BOOK: Inventing Iron Man
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