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Vital Signs with Dr. Sanjay Gupta

Doctor Specializes in Patients that Cannot Feel Pain; Researchers Map the Nervous System of the Fruit Fly; Surgeons Develop Methods to Advance Prosthetic Limbs. Aired 2:30-3p

Aired March 17, 2018 - 14:30   ET



[14:31:16] SANJAY GUPTA, CNN CHIEF MEDICAL CORRESPONDENT: Inhaling, perspiring, blinking -- these actions are all on autopilot. But behind these simple functions is a complex network made up of billions of cells telling our lungs to breathe, our skin to sweat, and our eyes to blink. This silent workforce is known as the nervous system.

This is "Vital Signs." I'm Dr. Sanjay Gupta.

The nervous system controls everything we do from the voluntary to the involuntary through a neurological tag team that races faster than the time it took me to finish this sentence. It's essentially the way that we control our bodies and communicate with the world around us.

So how does it work? What happens when it doesn't? And what does the future hold for the pathways that captain our bodies?

Our brain is always on, processing information from our surroundings and from within. It is our central command center. The brain is the first place to receive a signal. From there, it travels down the spinal cord and branches out the organs. For example, if you touch a hot stove, the nerves in the skin send a message of pain to your brain which then tells the muscles in your hand to move away. You can thank your nervous system for that speedy reaction. It is essentially our body's wiring made up of millions of microscopic messengers called neurons that send signals to parts of the body.

But what happens when our mainframes don't run properly? Movement, speech, memory and much more can be affected. According to the U.S. National Institute of Health, there are over 600 neurological diseases affecting more than a billion people around the world ranging from muscular diseases like multiple sclerosis to cognitive ones like Alzheimer's. And it can all start with a small disturbance in our wiring.

DR. CHRISTOPHER KLEIN, NEUROLOGIST, MAYO CLINIC: These small fibers are involved in regulating blood pressure as well as pulse, heart rate.

GUPTA: Dr. Christopher Klein is a neurologist at the Mayo Clinic in Minnesota.

KLEIN: Those are the sensory nerves. They look like little tree branches.

GUPTA: For 30 years he has been examining what goes on in our neural circuits.

KLEIN: Is it something in the brain or is it something in the spinal cord or is it something out from the spinal cord to the feet? It is a riddle that has a meaningful outcome if you can solve it.

GUPTA: He specializes in a very rare condition, the absence of pain.

KLEIN: I think that the best term agreed on right now is congenital insensitivity to pain.

GUPTA: Life without pain sounds like a blessing, but pain is our number one defense mechanism. Without it we can severely injure ourselves or we can miss warning signs of infections.

KLEIN: Some others would outline the story of many fractures, many visits to the emergency room, and sometimes even concern from health caregivers that there was some nefarious behavior on the parents when in fact it is that these poor kids could not feel any pain. The characteristic features are early corneal abrasions, early fractures, multiple injuries, including frequently injury to the skull. Patients very early in infancy may bite their lip to the point that it is mutilated or their tongue. Families are dealing with these problems really have to go through heroic efforts, including almost 24-hour supervision.

The thing that is important to understand about this disorder is they are not without feeling. So when they are exposed to the stimulus like a hot plate, they are feeling something, but they just don't have that natural recoil.

[14:35:01] GUPTA: Present from birth, congenital insensitivity to pain with anhidrosis, or CIPA, prevents pain fibers from firing signals to the brain. This genetic disorder is so rare its prevalence is unknown.

KLEIN: Just to put it in perspective, in a year of my clinic I might come to the diagnosis in only maybe one in a total year. So that is pretty rare.

GUPTA: Until 2006, little was known as CIPA and doctors didn't know how to test for it.

KLEIN: When we tested them we could not find any abnormalities, so we knew we had something different as did our colleagues throughout the world who were seeing these same very rare patients.

GUPTA: Later that year, a research team at the University of Cambridge identified one cause for CIPA, an abnormal gene inherited from both parents resulted in mutations of the SCN9A gene.

KLEIN: There seems to be an inherent problem with insensitivity to pain for this sodium to fire. But we now know it is not the entire story. GUPTA: Despite these findings there is still no cure.

KLEIN: So what we are really involved with is teaching the parents with the parents coaching how to recognize that feeling as a dangerous feeling. The analogy I like is a person who is colorblind. They can see, but they just don't know red from green. So for instance they don't drive through stoplights because they have learned that red is on the top and yellow in the middle and green is on the bottom. So these people if we keep working with them, they can eventually understand to avoid things that are very likely injurious.

GUPTA: Still Dr. Klein is hopeful that research will provide help not only for CIPA but also for those in pain.

KLEIN: We have a huge worldwide epidemic with pain. I see this as a huge opportunity to move things forward in understanding and hopefully coming to a more safe therapies for pain. In the United States, we are losing a huge number of people to opioid overdose, and so can we learn something here where we can develop a new drug that will not have the risk and help patients who are suffering with this?

GUPTA: Next, is it possible to map the entire nervous system? One lab in the United States is trying to unravel the wiring in our brains.


[14:40:34] GUPTA: You may have heard of the Human Genome Project. It's this international research effort that identified and mapped the more than 3 billion pairs of DNA which define all of us. Well, now researchers are trying to do the same with our nerves. Neuroscientists want to understand how the 86 billion neurons in our brains communicate to create behavior. But connecting the dots on even the most basic of signals in the common fruit fly is proving to be rather pesky.

What most people probably don't think twice about, the common fruit fly, Marta Zlatic thinks about all day. In fact they are the stars of her show at her Janelia Research Campus in Ashburn, Virginia. Zlatic's team is filming the reactions that fruit fly larvae, or drosophila, have to certain stimuli, like a puff of air for example.


GUPTA: This helps identify which of their 15,000 neurons make them recoil in response. These recordings are then helping them map the galaxy of neurons that produce behavior. It's the first step toward understanding how nervous systems work across the animal kingdom.

ZLATIC: I have always been fascinated by behavior and by the way in which the nervous system works. How can neural circuits generate, well, everything we are, our personalities, our decisions, our thoughts, our ability to be creative.

GUPTA: It is believed that the adult brain contains some 86 billion neurons. At birth many of these neurons are not yet fully connected to each other. As we are growing and learn new skills, new neural pathways are created in our brains. It is estimated that one neuron may connect with thousands of other neurons and these connections allow things like walking and typing and reading, for instance, to become second nature. Each of these actions have their pattern or computation made up of many specific neurons. But defining these neural connections is not so easy, even in an insect that has a fraction of the neurons that we do. Instead of 86 billion, they have just 15,000.

ZLATIC: The fruit fly larvae at the moment is a really ideal model system, and that is because the connections between the neurons are very small. It has a compact enough system that it is possible to image the entire nervous system with electro-microscopy. It is possible to manipulate genetically almost every single neuron type.

GUPTA: Lights off, camera on. Under these microscopes a turn to the left or a freeze offer clues into what ensemble of neurons creates a fight or flight behavior.

ZLATIC: So in a way neurons vote for each action. The nervous system has to implement a so-called very harsh and decisive computation, a winner-take-all computation, because a nervous system cannot afford be indecisive. It cannot give confusing commands. You cannot try to both sit here and walk at the same time.

GUPTA: Zlatic's team discovered which neurons correlated with each response and then reverse-engineered the experiment, activating the neurons to perform one way or the other.

ZLATIC: We go through thousands of neurons in this way, one at a time, and ask what happens if we activate this neuron?

GUPTA: You wouldn't think a common fruit fly would be so complex, but a few years of experiments in and they still only mapped two-thirds of its brain.

ZLATIC: Everything we do is in a very close collaboration with the lab of Albert Cardona. They are experts in mapping the wiring diagrams.

GUPTA: Cardona's maps look a little like a Jackson Pollack painting.

ALBERT CARDONA: Every tiny little black line that you are seeing here is a membrane of a little piece of the neuron.

GUPTA: But to his trained eyes, this wiring diagram helps explain how we do what we do.

ZLATIC: And this is a mesh that is the contour of the entire central nervous system.

[14:45:03] GUPTA: A symbiotic relationship. Cardona's maps then help Zlatic predict and text specific neural pathways.

CARDONA: And by advancing in this way piece by piece across this nervous system, we are putting together a comprehensive picture of how a brain works as a whole, which has never been possible before.

GUPTA: Their current research focuses on mapping dopaminergic neurons, which are involved in learning.

ZLATIC: We are manipulating specific circuits and while at the same time recording the output, in this case the firing of the dopaminergic neurons. If an animal expects to do something and get a reward, but it does not get the reward, then these dopaminergic neurons will be very, very active, and they will induce a memory so that in the future the animal can improves its behavior and its decision making. So whenever there is a mistake, then the nervous system learns, hopefully it does. Otherwise we would never improve our behavior.

GUPTA: These maggots squirming about may not appear to be a big deal, but these small creatures are helping to answer one of the biggest questions in modern neuroscience, how do our brains create behavior?

ZLATIC: I can definitely see this translating into our understanding of the human nervous systems because there are many human brain functions that are common to all animals. Decision making is one of them, choosing which action to do when.

This is almost significant.

If we can understand how decisions are implement and how learning happens, at least the types of the neurons and the motifs involved, one can start to thinking about selectively targeting them to improve disorders, and then, of course, learning and decision making.

GUPTA: Ahead on "Vital Signs," how technology is merging with nerves to change lives.


[14:50:32] GUPTA: Mapping how our neurons communicate, that's only a half the puzzle. Applying those findings to create medicine or to enhance surgical procedures, that could be the future of neural research. One area that's making strides in manipulating nerves is prosthetics, a technique that reassigns nerves endings is giving hope and control back to amputees.

Tiffany Johnson is a happy wife, and the mother of three.

TIFFANY JOHNSON, SHARK ATTACK VICTIM: You are very good. Yes, you are. You can be on this one for now and then you guys can trade.

GUPTA: As most working moms do, she struggles with the day to day sometimes.

JOHNSON: Give Natalie a chance, because she won't be on for long. Are you ready?

GUPTA: But not too long ago she was struggling for her life.

JOHNSON: We were on a cruise. We had decided early on in the cruise that we wanted to for sure snorkel in Nassau because it was really good snorkeling. And so we went out to the reef, I was just staring at the fish and enjoying the view. And I felt like I had bumped into something. Like a tug on my arm. And I remember even just thinking, oh, what did I bump into, and then when I turned I was literally face- to-face with a shark.

Fear took over, and it just dawned on me what was going on. My whole arm was in his mouth. And I remember hearing the sound of my screaming through the snorkel tube. My body wanted to give up. I was seeing almost like a movie reel of my kids and I remember just thinking, no, we are not going there. And then when I yanked my arm finally that last time, his jaws opened, and I pulled my arm out, and it was just gone. It was a mangled stump.

GUPTA: She had her first operation in Nassau, but they could only do so much. She needed to get back home.

JOHNSON: We had the minister of tourism in the Bahamas involved and the embassy involved and customs involved. They were all trying to figure out a way to get us back to the U.S. The problem with was we didn't have passports with us.

GUPTA: With the help of the pastor back home in Charlotte, North Carolina, she was privately medevacked off of the island.

JOHNSON: It was just miracle after miracle after miracle.

GUPTA: But it has been a tough journey since, relearning how to do one simple task like eating.

JOHNSON: It is difficult to keep it steady.

GUPTA: But Johnson has not let it slow her down.

JOHNSON: Once I have my prosthetic, that will help a ton, because it will give me another hand to function with.

GUPTA: She is a poster child for positivity.

UNIDENTIFIED MALE: How are you going with the left hand?

JOHNSON: I am decent. The hardest part is holding the paper honestly.

GUPTA: And also the perfect candidate for the cutting edge prosthetic that she can control with her mind.

JOHNSON: I am ready to rock 'n' roll.

GUPTA: Today, Johnson is receiving her first smart arm an Ortho Carolina's Reconstructive Center for Lost Limbs. Doctors Ryan Loeffler and Glenn Gaston are two of a few surgeons worldwide pioneering a state of the art surgical procedure.

DR. RYAN LOEFFLER, SURGEON: He actually has implantable sensors in all the different muscles.

GUPTA: Enabling the nervous system to communicate with artificial limbs.

LOEFFLER: One of the things that we're doing surgically is trying to improve the interface between the human being and the newer technologies that are out there. So by rewiring their nervous system, we can actually allow them to interface with the prosthetic in a new way that is more intuitive.

GUPTA: One of these ways is called targeted muscle reinnervation, or TMR. The surgery transfers nerves that control the amputated limb and rewires them into alternative muscle sites.

LOEFFLER: So when you go to do something, for example to raise your thumb, your brain sends that signal down your spinal cord through a network of nerves that comes down the forearm and into the muscles of the thumb and the hand.

[14:55:00] When that hand and forearm even are lost, you still have that same signal that can be sent down, but it doesn't have a target. So the idea of target is taking a different muscle to take the nerve ending and to implant that into a nerve that's going to that muscle.

UNIDENTIFIED MALE: Beautiful. Relax.

LOEFFLER: Now it does have not a dead end, it has a muscle, so it can cause a contraction of the muscle. And when the muscle contracts, it generates an electrical signal that can be detected by a sensor that is on the skin. And that signal can then be transduced into a prosthetic to allow the thumb functioning to occur.

DR. GLENN GASTON, SURGEON: We do these nerve transfers. The brain is sending the normal signal downstream, so they just think close my hand and they close their hand. Wo we have patients now who put on their limbs for the first time and within an hour are performing all of the functions that we can ask it to perform.

The real unique challenge with Tiffany's was the very short residual limb that we had to work with and the very small muscles. We had to be fairly creative with which nerves were rerouted to the few muscles that we had remaining. But she has been an incredible person through it all and I think her drive and her spirit to get through everything is really exemplary, and she has rubbed off on a lot of our other patients.

GUPTA: Johnson has a lot the be thankful for, but above all, she still credits her faith.

JOHNSON: A couple of days after the attack and I started reading Psalm 18, and I couldn't keep it together, where it says the grave wrapped its ropes around me, death itself stared me in the face. That is exactly what happened. I was staring face-to-face with that shark, and then later he reached down from heaven and he drew me out of deep waters. I just couldn't -- I was just in awe of reading this, and I'm thinking, oh, my gosh, this is my story.