Pioneering Prosthetics - Targeted Muscle Reinnervation Surgery Hands Back Control

21 February 2011
Presented by Ben Valsler, Dave Ansell.

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In this NewsFlash, we'll find out how an isolated population of people in Ecuador may hold the genetic key to a disease free life, and how hibernating bears slow their metabolic rate far more than expected, and may one day help us to reach for the stars! Plus, they mysterious Death Valley rocks that seem to move around on their own, and how re-routing nerves can allow amputees to move a prosthetic limb more naturally than ever before.

In this episode

Structure of the Growth Hormone Receptor (GHR) protein.

00:29 - Dwarfism Gene - Key to a Long and Healthy Life?

An isolated population of people in Ecuador could hold the genetic key to a long and healthy life, according to research published in the journal Science Translational Medicine this week...

Dwarfism Gene - Key to a Long and Healthy Life?

An isolated population of people in Ecuador could hold the genetic key to a long and healthy life, according to research published in the journal Science Translational Medicine this week.

It's known that mutations in growth signalling pathways can extend life span and reduce genetic damage in model organisms like yeast and nematode worms, and even reduce insulin resistance and cancer rates in mice.

Structure of the Growth Hormone Receptor (GHR) proteinTo find out what effect mutations in similar genes may have on humans, Jaime Guevara-Aguirre at the institute of Endocrinology, Metabolism and Reproduction, in Quito, Ecuador; Valter Longo at University of Southern California, and colleagues, have studied a group of 99 related people who all displayed a mutation in the Growth Hormone Receptor or GHR gene - most of them having the E180 mutation, where the resultant protein lacks eight amino acids, and as such cannot fold into the correct shape.  As a result of this mutation, their growth is limited.

The subjects themselves have been observed since 1988, and information on illness and death has been collected for a further 53 GHR-deficient relatives, and 1606 relatives of the cohort that were not affected by GHR-deficiency.  This allowed the researchers to look at causes of illness and death in the two populations to see if there were any significant differences.

Cancer accounted for 17% of all diseases, and 20% of deaths in the unaffected relatives, but was not recorded as a cause of death for anyone in the GHR-deficient population.  Likewise, there were no reported cases of diabetes in the affected population, and blood tests revealed significantly lower levels of insulin - this tells us that something about this mutation increases insulin sensitivity.  However, there was no evidence of an extended lifespan, probably due to the high proportion of deaths caused by non-age-related causes like convulsive disorders, alcohol toxicity and accidents.

To try to explain why this might be, the researchers took human cells and incubated them with serum from either the GHR-deficient subjects or their non-affected relatives, before exposing these cells to a highly oxidising solution of hydrogen peroxide.  While individual cells incubated with the GHR-deficient serum showed less DNA damage, there was also higher levels of apoptosis, or programmed cell death, amongst these cells. This suggests that the cells tend to self-destruct rather than accumulate DNA damage.

The authors suggest that their results "provide a foundation for further investigation into the role of drugs blocking the GHR to prevent or reduce the incidence of cancer, diabetes, and other age-related diseases."

Electrically Neutral Atom image of the earth's surroundings taken by the IBEX probe

03:48 - Picture of Earth's plasma tail

First picture of the Earth's plasma tail has been taken, and it is more dynamic than expected.

Picture of Earth's plasma tail

The northern lights have recently been in the news this week, and they are caused by the solar wind, which is made up of energetic charged particles thrown off the sun being trapped by the earth's magnetic field then crashing into the atmosphere exciting the air molecules, making them glow. Unfortunately for those trying to understand this the moving charged particles are effectively an electric current, and electric currents produce a magnetic field, altering where the particles path, changing the magnetic field etc.

To make it even more difficult, the charged particles are essentially invisible as they fly through space, and the effect they have on the magnetic field is only measurable by actually putting an instrument in that position, and there is a limit to the number of satellites you can use at once.

The Interstellar Boundary Explorer or IBEX satellite was actually designed to look at the heliopause which is where the sun's magnetic field and solar wind becomes overwhelmed by the galactic solar wind. At this junction sometimes a charged nucleus will pick up electrons becoming a neutral atom, these are then unaffected by magnetic fields, and will continue in a straight line, only affected by gravity. So if some of them reaches IBEX satellite you can measure the direction they came from. IBEX has built up some interesting pictures of the heliopause, but sometimes in its orbit it looks at the earth where something very similar is happening where the earth's magnetic field is being overwhelmed by the sun's magnetic field.  

The result is an admittedly low resolution image of the magnetic tail or plasma sheet that streams out behind the earth.  Dave McComas who is the principal invetigator on the mission has published two images of this tail, and they show it is a very dynamic place with an image from one orbit showing it as a smooth tail, but the second has a lump of plasma being pinched off, much closer to the earth than current theories were expecting, possibly because the tail was being squeezed by the solar wind.

Understanding these processes is becoming more important as the sun is moving into a more active part of its 11 year solar cycle and solar storms have knocked out satellites, telegraph and even electricity grids, and it is an interesting example of an instrument designed to investigate something very abstract being used much closer to home.

ENA map from IBEX probeENA map2 from IBEX probe

Retired Staff Sgt. Bradley K. Gruetzner explains his prosthetic arm to servicemembers at Al Faw Palace, Camp Victory, Iraq, June 21.

06:33 - Targeted Muscle Re-Innervation Pushes Prosthetic Performance

When someone loses a limb, although it's possible to replace the missing part with a prosthesis, making it move is another matter entirely. But a technique being pioneered at the University of Chicago could change that...

Targeted Muscle Re-Innervation Pushes Prosthetic Performance
Dr Todd Kuiken & Martin Baechler, Rehabilitation Institute of Chicago; Sgt. Glen Lehman

Ben -   When somebody loses a limb, although it's possible to replace the missing part with a prosthesis, making it move is another matter entirely.  But a technique being pioneered at the University of Chicago could change that.

Todd Kuiken has been experimenting with targeted muscle re-innervation surgery, and what he does is to take the nerves that used to supply the severed body part and reroute them into a piece of muscle further up the limb.  Now, when the patient thinks about moving the missing body part, the rewired muscle will change its activity instead.  By using electrodes to eavesdrop on that activity, it can be used to control the motors of a prosthetic arm.  

Chris Smith met with Todd Kuiken and his patient Sgt. Glen Lehman, who's actually undergone this procedure, at the AAAS Conference in Washington DC...

Todd -   Our big challenge is how to control an artificial limb.  You lose your arm and we can make robotic limbs, but how do you tell it what to do?  So we've developed a technique that we call targeted muscle re-innervation where we've developed a neural interface to capture what the person wants to do with their limb.  Essentially, the way it works is we take the major nerves that used to go to the amputated arm, and they're still functional.  They send motor commands, and if you'll stimulate them, you'll feel the missing arm.  So we take those nerves and we transfer them to some spare muscles in the residual limb.  Those nerves will then grow into those muscles and when they - Glenn for example - thinks to close his hand, now his medial biceps contracts, and we can detect a signal from that muscle contraction and tell his artificial hand to close.  In this way, we can get much more function and its intuitive.  He thinks to close his hand.  His hand closes.

Retired Staff Sgt. Bradley K. Gruetzner explains his prosthetic arm to servicemembers at Al Faw Palace, Camp Victory, Iraq, June 21.Chris -   Glenn, can you give us a demonstration?

Glen -   I can.

Chris -   First of all, talk us through what actually happened to you and how long have you been using the prosthesis you've got?

Glen -   November 1st, 2008, I lost my arm.  I was on a combat patrol in Iraq, they threw an RKG-3 hand grenade at my truck, it penetrated the armour and separated or amputated my arm.  After that, I was evacuated and sent through Walter Reed where I received treatment.  Dr. Baechler and Dr. Kuiken came to me and asked me if I would be a candidate for the targeted muscle re-innervation surgery, and then just this last week, I received this arm or went out to IRC in Chicago, and trained with them with this arm.

Chris -   Can you show us what it can do?

Glen -   I can raise them lower the elbow, I can rotate the hand, so it's in our out.  I can open and close the hand, and I can flex the wrist either in or out.  Those movements were all controlled by me, thinking about my phantom limb.

Chris -   So you're thinking about moving fingers that you no longer have, but are present on the prosthesis obviously, and those thoughts are being translated into what the prosthesis does.

Glen -   Yes, that's correct.

Chris -   Is it easy to learn to do?

Glen -   I've only used this arm for two weeks, so it was very easy.

Chris -   What sort of resolution of movements can you manage?  If I gave you some peas to pick up, could you do that?

Glen -   I believe I could, yes.  The larger the item, the easier it is to actually grasp.  I mean, a bottle of water or something like that is easier.  It's very hard to pinch things off the table.

Chris -   If you didn't have this, what would you have instead and in what way has this enriched your life?

Glen -   I would just have a conventional arm.  I would be able to operate the elbow and the hand, but it wouldn't be simultaneous.  I would only be able to cycle through each thing by switching co-contracting muscles.  So it's like the comparison between a minivan and a sports car.  It's different categories.

Chris -   Martin [Baechler], you had to do some of the surgery to make this feasible.  What's actually involved in implementing a prosthesis like this in terms of actually rerouting the nerves to muscles and so on?

Martin -   Well the performance of the surgery is actually very simple.  The anatomy is predictable and the procedures of transferring the severed nerve to a healthy piece of muscle is quite simple.

Chris -   How long does it take patients to actually begin to use and work one of these prostheses?

Martin -   Well since we put the severed nerve so close to the new muscle, it only takes a couple of months before we start getting some contraction of the muscle.  It may take six months or maybe even a year before it fully matures and the connection between the brain and that newly innervated muscle is plateaued and it's what's going to be.

Chris -   Just coming back to you Todd, in terms of actually how the process works, so there are actually, physically, electrodes which are listening to what the muscle is doing when Glen thinks what he wants to do.

Todd -   That's correct.  We have sets of little electrodes that are like antennas, listening to his muscles.

Chris -   If he had had his injury 20 years ago compared to very, very recently - you got to him when it was a fresh injury, would that have made a difference to whether this could be done?

Todd -   It may have.  The answer isn't really known.  We're comfortable doing the surgery for 5 or 10 years after injury in a younger patient, but there may be a limit someday that we'll find, that we don't want to cross over.  We know that the nerves are still viable for decades after the injury, but how good they are at regenerating is a question.

Chris -   And what about sensation because at the moment, he obviously can see what he's doing, but he can't feel what he's doing.  What about taking it into that domain next?

Todd -   We have been able to provide hand sensation for some of our amputees.  What we do is cut the nerve to the skin over these nerve transfers and then the hand sensation nerves will grow into this residual limb skin.  So when you touch it, it feels like your touching the missing hand.  It's very exciting for us because it gives us potential of putting sensors in the prosthesis to see when you touch something or how hard you're squeezing and feed that information back, so that the patient feels that they're getting that touch or pressure on their missing hand.

Ben -   And if this prosthetic is like a sports car compared to the traditional minivan, then just imagine what it would be like when you can feel what your prosthetic is touching as well.  That was Todd Kuiken, Martin Baechler and Sgt. Glen Lehman, speaking to Chris Smith at the AAAS Conference in Washington this week. 

 A young male American black bear after emergence from hibernation. The bear is part of the hibernation research conducted by Øivind Tøien, research scientist with the Institute of Arctic Biology at the University of Alaska Fairbanks, and first author...

12:50 - Black Bears may send us to the Stars

Alaskan black bears do not hibernate in the same way as other, smaller, mammals and an understanding of how they achieve their winter’s rest may help improve medical care and open the door to deep space travel...

Black Bears may send us to the Stars

Alaskan black bears do not hibernate in the same way as other, smaller, mammals and an understanding of how they achieve their winter's rest may help improve medical care and open the door to deep space travel.

Hibernation is a very useful behaviour in challenging environments.  By slowing the metabolic rate, an animal is able to cut its energy costs dramatically and survive a harsh winter on bodily reserves alone.  In general, metabolic rate slows by 50% for every 10 degree Celsius drop in body temperature.

A young male American black bear after emergence from hibernation.Most of the hibernating animals studied so far, generally small mammals like hedgehogs, typically reduce their body temperature to around their freezing point for weeks on end, with occasional breaks when the body temperature rises to normal for a day or so.  These breaks are thought to allow opportunities to repair any nerve damage resulting from the hibernation itself, and account for around 80% of the animal's energy costs during hibernation.

Larger animals, like bears, have been harder to study due to technical limitations.  Writing in the journal Science, researchers at the University of Alaska Fairbanks, along with colleagues from Stanford University, have had a unique chance to study five Alaskan bears captured by the Alaska Department of Fish and Game as nuisance animals.   Øivind Tøien and colleagues allowed the bears to hibernate in artificial dens, which were kitted out with infrared cameras, activity detectors and other remote sensing devices, and monitored them throughout five months of hibernation.  They measured oxygen concentration in the air, as a marker of metabolic rate, and surgically implanted radio transmitters in the bears to report on temperature and heart activity.

This allowed them to see that black bears reduce their metabolic rate to just 25% of it's normal level, despite staying warm - 33 degrees on average.  Their heart rates dropped from around 55 to just 14 beats per minute, and showed marked sinus arrhythmia - variation in frequency relative to breathing.  This suggests that the bears have mechanisms to divorce metabolic rate from body temperature, allowing them to spend long periods without eating, drinking or defecating, but without the need to be cold.  On leaving hibernation in spring, the bears did not instantly return to a high metabolic rate.  This instead developed over the next two to three weeks.  Also, unlike humans, who lose muscle and bone during a period of inactivity, bears do not seem to suffer this loss.

As well as improving our understanding of how large animals cope with harsh conditions, this could help us to develop novel medical interventions.  Brian Barnes, the senior author of the study said:

"If we could discover the genetic and molecular basis for this protection, and for the mechanisms that underlie the reduction in metabolic demand, there is the possibility that we could derive new therapies and medicines to use on humans to prevent osteoporosis, disuse atrophy of muscle, or even to place injured people in a type of suspended or reduced animation until they can be delivered to advanced medical care."

Picture of two rocks on Racetrack Playa in Death Valley. Notice the mysterious groves leading away from the stones.

15:54 - Mysterious death valley moving rocks

Mysterious moving stones in a Death Vally lake bed may have been solved.

Mysterious death valley moving rocks

In almost perfectly flat dry lakebed at the upper end of Death Valley there  some strange rocks known as 'sailing stones'  are dotted about the otherwise almost smooth lake bed, some of them weigh up to 36kg, but behind them are tracks sometimes tens of metres long as if they were moving. The tracks can be straight or zig zagged and some of the stones have been marked and their positions seem to change relative to stakes put in the ground, but noone has ever seen a stone move.

The movements seem to occur on the rare occasions whern the lake bed is covered with a shallow layer of water, there is a strong wind and the temperature is very low. Both ice bergs and winds which can reach 90mph only a couple of inches above the lake bed have been suggested as ways of moving the stones but neither has been decisive.

Sailing Stones
Picture of two rocks on Racetrack Playa in Death Valley. Notice the mysterious groves leading away from the stones. © Maveric149

Ralph Lorenz, a scientist at Johns Hopkins University has come up with a new explantion, a neat combination of both. The lake floods a couple of inches deep, and as it does so a small ice berg forms around the stone, the water level increases slightly and beacuse ice floats this gives the stone lift, reducing the friction with the ground. The high winds are then able to push the stones along forming the long tracks. They have done some exeriments which support their hypothesis, though it will be hard to know what is happening for sure until someone actually sees one moving.

This is a lovely mystery, but studying areas like the racetrack playa may be useful in understanting places like the shallow lakes on Saturn's moon Titan, where there are some hydrocarbon lakes which seem to occasionally dry out.

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