The New Medicine: Hacking our Biology
The New Medicine: Hacking Our Biology is part of the series “Engineers of the New Millennium” from IEEE Spectrum magazine and the Directorate for Engineering of the National Science Foundation. These stories explore technological advances in medical inventions to enhance and extend life.
- After a Stroke: Regaining Muscle Control
- Synapse Microarray Will Hold Neurons in Place
- Paraplegic Patient Tests a Medical Exoskeleton
- Brain-Computer Interface for Spinal Cord Injury
- Artificial Materials to Repair Damaged Nerves and Disappear
- Harvesting Blood From Limpets for a Cancer Vaccine
- A Revolutionary Cancer Treatment Device Inspired by the Mosquito
After Stroke: Regaining Muscle Control
Susan Hassler: Strokes are the largest cause of adult disability in the United States. A person has a stroke, on average, about every 35 seconds. That adds up to around 800 000 people a year. Many stroke survivors are left with limited control over their bodies and long recovery periods. To regain muscle control, stroke patients must retrain their bodies and brains to connect by doing many of the same movements over and over. To make this tedious rehabilitation work more fun, researchers at University of California, Irvine, have invented a new device. It mixes movement with music, as Caitlan Carroll reports.
[ambient sounds of talking in laboratory]
Caitlan Carroll: Josh Gray sits in a laboratory filled with computers and robotic-looking machines. He’s part of a sample group of stroke survivors testing out a new rehabilitation device at the University of California, Irvine, or UCI. As I walk into the lab, the first thing I notice about Josh is his big, big laugh.
[ambient sound from laboratory; laughing]
Caitlan Carroll: The second thing I notice is that Josh is unable to open his right hand wide enough to shake my hand. So we do a kind of fist bump instead. At 16, Josh was a typical teenager. He played basketball and liked hanging out with friends. But on the morning of June 9, 2009, life changed. He woke up and couldn’t feel part of his body.
Josh Gray: Something happened, like I couldn’t move my right arm. Dad comes in and says, “Josh, what happened? You’re supposed to be at school.” And I couldn’t say anything. I was impaired.
Caitlan Carroll: Josh had injured his knee while playing basketball. The doctors think that this injury may have created the blood clots that eventually traveled to his brain and caused a stroke as he slept. Now Josh is 19 years old and still struggling to reclaim movement on the right side of his body. Nizan Friedman checks Josh’s grip on his right hand.
[ambience in laboratory; talking: “Good work. That hand strength is really getting there.”]
Caitlan Carroll: Friedman, a biomedical engineer at UCI, is one of the designers of the product Josh is testing. Friedman says even though Josh is unusually young to have a stroke, his physical problems are similar to those of many patients.
Nizan Friedman: When someone experiences a stroke, it normally occurs on one side of their body, and essentially what happens with a stroke is a part of your body, a part of your motor cortex, gets destroyed. So the goal is for the brain to reorganize itself so it can now attach new parts of the neurons to the damaged areas.
Caitlan Carroll: Friedman says to build up those neural connections, a stroke patient must do repetitive exercises over a long period of time.
Nizan Friedman: Essentially, the more you try to work on it, the more it kind of happens. So when you really try to move your arm a thousand times, eventually your brain will get it.
Caitlan Carroll: But trying to move your arm a thousand times when it doesn’t want to can be frustrating and boring work. That’s why Friedman and UCI professors Mark Bachman and David Reinkensmeyer created a device called the Music Glove. It’s designed to encourage stroke survivors to make the kinds of hand movements they need in daily living—so they can button a shirt, for instance.
Nizan Friedman: The way this device works is the patient using it has to put on a glove, a sensorized glove, that they need to make specific movements with. And we have this device plugged into a PC, and when they make a movement on the device, they are also using it as a controller for a Guitar Hero–like game.
Caitlan Carroll: The Music Glove is made of a lightweight, stretchy material and has sensors in the fingertips. A stroke patient can easily attach it with Velcro strips and then boot up the video game on any computer. The video game that goes with the Music Glove is called Frets on Fire. The computer screen shows a guitar fret board. As the music starts, colored dots appear on different strings at different times. A player must move each finger in the glove like he’s playing notes on a guitar. A player gets points when he moves the right finger at the right time. Josh Gray demonstrates for me. First he picks a song. Then he puts on the glove...
Caitlan Carroll: ...and starts up the game.
Caitlan Carroll: So, do you have a favorite song? Is that it?
Josh Gray: Yeah, that is it—“I Walk the Line,” by Johnny Cash.
Caitlan Carroll: Nice! I like it too. Cool. So, we’re going to see how this works.
Josh Gray: All right—brace yourself [laughs].
Caitlan Carroll: Josh is smiling while he plays. But when Josh first tried the Music Glove, he was a little doubtful.
Josh Gray: My first reaction was, what can I do with this? As the procedure kept going, I started to move my right thumb and my index finger, and I thought, Hey, this is pretty cool. And at the end, I was, like, “One more song, one more song...two more songs...” And I could just not let it go.
Gary Gray: In the month—six weeks—we’ve been involved, we’ve already seen drastic improvement in his right hand.
Caitlan Carroll: Josh’s dad, Gary Gray.
Gary Gray: And knowing that the brain and the hand are talking and responding to one another has really been just extremely eye opening.
Caitlan Carroll: Like many families, Josh and his dad, Gary, have limited health insurance. So the Music Glove is appealing because it’s a potentially inexpensive form of therapy. UCI’s Nizan Friedman says he hopes that with low-cost devices like the Music Glove, patients like Josh will be able to easily and cheaply continue their rehab after returning home from the hospital.
Nizan Friedman: With this device, we are really trying to target it to the at-home setting and also the clinic, so we would like this device [to] cost hundreds rather than thousands of dollars.
Caitlan Carroll: Nizan says the music is a key element to the device’s possible success. He says studies have shown listening to music helps stimulate the brain’s cortex—and also, the stroke patients like it. Josh Gray already has his favorite set list.
Josh Gray: Oh! Johnny Cash, Nirvana, Ray Charles...
[Ray Charles singing: Well, I got a woman, way over town that’s good to me...oh yeah]
Caitlan Carroll: When the Music Glove goes on sale, in a year or more, Gary wants to buy it for Josh. He hopes this kind of easy-to-use technology may help his son take some big steps toward a more independent future.
Gary Gray: That’s our big end game: Is Josh to feel that independence and to know that he is independent, working his way through his life, you know, paying his own bills, having his own place, driving his car, things of this nature. It’s all geared toward being independent again.
Caitlan Carroll: And for Josh, the thought of an independent future...well, that’s music to his ears. In Irvine, California, I’m Caitlan Carroll.
Photo: Caitlan Carroll
Synapse Microarray Will Hold Neurons in Place
Susan Hassler: Here’s a question for you: What do Facebook and neuroscience have in common? Give up? It’s a belief that you are your connections. Samuel K. Moore went to MIT, in Cambridge, Massachusetts, to report on the latest research on Alzheimer’s disease.
Samuel K. Moore: Neuroscience has shown more and more dramatically that how the cells in your brain connect to each other is the secret to what we think, feel, and do—and how we remember what we thought, felt, and did. Unfortunately, it’s also finding that when those connections are interrupted...disease results. Those connections—from one neuron to another—are called synapses, and they’re crucial to information processing in the brain.
Mehmet Fatih Yanik: Many neurodegenerative diseases—like Alzheimer’s, for instance—are basically either effecting synapses or are caused by malfunctioning synapses. So a lot of pharmaceutical companies today are interested in finding drugs that can enhance synaptic strength and modulate it.
Samuel K. Moore: That’s Mehmet Fatih Yanik, a professor of biomedical engineering at MIT. He and his students have built a device that could help find drugs to enhance and modulate synaptic strength a whole lot quicker—possibly compressing years of searching into just a few months.
Samuel K. Moore: The device is called a synapse microarray. Using high-powered lasers and some of the same techniques Intel uses to make microchips, Yanik and his students built microscopic structures designed to hold neurons in place. Each neuron, when placed on the chip, is forced to grow a projection, called an axon, through a microscopic channel.
Samuel K. Moore: The channel leads to a chamber holding a target cell. Will the neuron connect with its target?
Samuel K. Moore: Will the connection be strong...or weak?
Samuel K. Moore: A strong or weak connection is determined by the chemicals with which you surround the synapse. Yanik’s microarrays let you try out a lot of different chemicals in a short amount of time.
Mehmet Fatih Yanik: A machine can go and measure the synaptic strength much faster and much more reliably than any existing technology.
Samuel K. Moore: Yanik says they can measure synaptic strength 10- to 100-fold faster.
Mehmet Fatih Yanik: This makes this technology much faster in terms of screening large chemical libraries looking for specific chemicals that can enhance synapses.
Samuel K. Moore: These chemical libraries can be quite large, containing a million or even 3 million chemicals. So speed is very important. Let’s say [you] want to screen a medium-size of library of 100 000 chemicals. That would take several years, using the technologies pharmaceutical companies use today.
Mehmet Fatih Yanik: This is too long of a time frame, because you have to do so many other things to develop a drug. You cannot spend a few years trying to hunt for the lead chemicals. With our technology, we can do the same screen in just a matter of a few months.
Samuel K. Moore: Finding a chemical that can alter the strength of neural connections could be key to fighting or at least slowing down diseases like Alzheimer’s. In neurodegenerative diseases like Alzheimer’s, the brain is constantly losing neurons—constantly losing connections.
Mehmet Fatih Yanik: The capability to enhance the processing power of the intact brain by inducing neurons to make more synapses can actually compensate for the functional decline in Alzheimer’s.
Samuel K. Moore: He might know the needs of doctors and drug developers well, but Yanik isn’t either. He’s not even a neuroscientist. He’s a laser guy. He spent the early part of the decade working on one of the hottest physics discoveries of its time—slowing down and even stopping the fastest thing in the universe, light.
[whistle with pitch decreasing to nearly 0 hertz]
Mehmet Fatih Yanik: After a while, I got bored with what I was doing at the time.
Samuel K. Moore: Sorry—you got bored with stopping light?
Mehmet Fatih Yanik: Yes. You could say that.
Samuel K. Moore: So Yanik trained his lasers on the maladies of the brain. His first work put a new tool in the hands of scientists trying to figure out how brains reestablish connections after injury. Working with neuroscientists at Stanford University, he turned one of the most extreme lasers available into a scalpel so precise that it could cut the connection between two neurons without damaging anything else.
The laser is called a femtosecond laser, because it fires pulses of energy that last for a few tens of femtoseconds. What’s a femtosecond? Glad you asked. Here’s Mark Scott, a Ph.D. candidate in Yanik’s lab.
Mark Scott: My favorite way to describe this is if you think of a jet fighter on afterburner, it will move less distance than [a] hydrogen atom in the time that a femtosecond passes. So, this laser has a pulse length of about 100 femtoseconds. So I think that it moves a few hydrogen atoms in that time.
Samuel K. Moore: Now they’re using that laser to help build better synapse microarrays. The brain has a very highly organized architecture, so it can fail at the level of cells or at a higher level—the level of circuits.
Yanik’s lab is at work building much more complex arrays that contain neural circuits which are able to simulate simple processes we know go on in our own brain, such as memory and feedback. They’ll use the circuits to test new drugs. And with these better arrays, they hope, will come better treatments. I’m Samuel K. Moore.
Photo: Christine Daniloff/MIT
Paraplegic Patient Tests a Medical Exoskeleton
Susan Hassler: The word exoskeleton may make you think of bugs and your high school biology class. But these days, exoskeletons are also the cutting-edge robotic suits that people can strap onto their bodies to augment their normal abilities. Some exoskeletons are being developed for the military, to let soldiers carry heavier loads or walk farther. Another kind allows paralyzed people to stand up and walk again. Eliza Strickland visited a hospital to watch a paraplegic patient try using a medical exoskeleton.
[ambient laboratory sounds; man at clinic: “Okay, you ready?”; sounds of Robert Woo walking in the exoskeleton]
Eliza Strickland: We’re in a crowded rehab room at New York City’s Mount Sinai Hospital, where Robert Woo is taking slow, halting steps. That’s pretty remarkable for a man who is paralyzed from the waist down. Woo lost the ability to walk four years ago when he was injured in a construction accident.
Robert Woo: It was a crane accident in New York City. It happened December 14, 2007. I was the architect for the new Goldman Sachs world headquarters in lower Manhattan. I was in my trailer, finishing off a site visit. And 7 tons of steel fell from about the 25th or 30th floor onto my trailer. I was crushed from [the] neck down.
Eliza Strickland: Now Woo is on his feet, held up by a pair of sleek, mechanical legs that are strapped to his own legs. This exoskeleton device does the walking for him by supporting his weight and bending his knees and hips in sequence to produce natural-looking steps. Leading U.S. rehabilitation hospitals will soon be using these exoskeletons, which make it possible for spinal injury patients to put on their walking shoes. Robert Woo is trying out the device, which is called the Ekso, during its one-week demonstration at Mount Sinai. He says he was plenty nervous at first.
Robert Woo: It was scary standing up, because I didn’t know what to expect. I didn’t have any confidence in it. It was a new device; I was worried about falling or injuring myself.
Eliza Strickland: But Woo is making rapid progress. During his first 1-hour session at the rehab clinic, he trained with a wheeled walker. By his third session, he is already marching up and down the room using two walking sticks, or crutches, for balance.
[laboratory ambience; people at clinic talking: “Crutches forward…crutches forward…. Nice job…. That was pretty good. You looked like you trusted it there a little bit”]
Eliza Strickland: The Ekso is built by a Berkeley, California, company called Ekso Bionics. I visited the company’s headquarters on a tree-lined suburban street in West Berkeley, where modest bungalows alternate with industrial buildings. Inside the company’s cavernous warehouse, dozens of pairs of legs dangle from ropes like the bottom half of a robot army.
Nathan Harding: This is both our manufacturing space and our engineering test space. We get to do all sorts of crazy things with Eksos right here.
Eliza Strickland: That’s Ekso Bionics cofounder Nathan Harding, casually dressed in jeans and a T-shirt, who shows me around. We stop by one Ekso system that is undergoing a durability test, taking step after step in the empty air. Harding explains how the system works.
Nathan Harding: The Ekso is essentially a pair of robotic legs that you strap on. It both carries its own weight, and it provides torque to the joints of your legs, just like your muscles would, to allow you to stand up and carry your weight on your bones the way someone who hasn’t had an injury would. It uses servomotors at the hips and knees to move the body in a natural gait.
Eliza Strickland: The plastic and aluminum legs do the heavy lifting, but exoskeleton users like Robert Woo have a lot to learn about making the devices work for them. Woo has to balance his torso above the robotic legs and shift his weight from side to side in preparation for each step. He also manages two walking sticks, which help with balance. Because a patient must have upper-body strength to use the Ekso, this technology can’t help all paralyzed people. But Ekso Bionics does plan to expand its customer base beyond people with spinal cord injuries and hopes to start working with both multiple sclerosis and stroke patients soon.
Nathan Harding: There are more than 2 million people in the U.S. who use wheelchairs. If you can even get a small percentage of those people up and walking in Eksos, you’ll have done a lot of good.
Eliza Strickland: In the current Ekso system, the physical therapist uses a remote control to trigger each step of the robotic legs. But with the next-generation model, users will have upgraded walking sticks with embedded motion sensors to control their own steps. Moving the right crutch forward signals the left leg to step forward and vice versa. In time, says Harding, even that user control system will be outdated.
Nathan Harding: There’s a lot of talk about long-term solutions and direct interfaces to [the] brain, to other parts of the nervous system. Which of course are extremely exciting, and they’re inevitable in the human exoskeleton business, but the key right now is to pick a path that gets people up and walking as soon as possible and lets them do what they need to do.
Eliza Strickland: Can exoskeletons really change people’s lives? Back in New York, I talked with Dr. Kristjan Ragnarsson, chairman of the department of rehabilitation medicine at Mount Sinai Hospital. He’s been in the business a while.
Kristjan Ragnarsson: I have been treating people with spinal cord injury for almost 40 years. The first thing that occurs to most of them is whether they will walk again. And as their physician, I always have to address that question.
Eliza Strickland: Over the years, Ragnarsson says he’s seen a wide range of high-tech gadgets that were intended to let paralyzed people walk again. All of them failed, he says, because the patients had to exert far too much energy to walk in the devices.
Kristjan Ragnarsson: It’s like if you were running the 100-yard dash all the time—they are completely exhausted after just a few steps.
Eliza Strickland: Ekso is different, he says, because it uses external power to help the patients move their paralyzed limbs.
Kristjan Ragnarsson: As a physician for these patients, I’m hopeful that that will indeed reduce the energy consumption to the extent that they will be able to ambulate or walk. That doesn’t mean they won’t need training. They will need extensive training, because to operate this kind of system successfully, you need to be pretty nimble, pretty smart, highly motivated, and in good shape besides your paralysis. But I’m optimistic, actually, that this will work.
Eliza Strickland: Ekso Bionics plans an ambitious rollout. First comes the device that will allow patients to train at rehab hospitals. Later on, the company will introduce a version that can be used for at-home physical therapy. Robert Woo says he thinks the Ekso will have both physical and mental benefits for him.
Robert Woo: It definitely will make a difference in my life. I already feel very energetic. I think the biggest thing is the emotional feeling of being able to stand and walk. With this bionic system, it makes you feel like you can walk again—like you used to, before your accident.
Eliza Strickland: Within the next few years, Ekso Bionics plans to have a version ready for everyday use—a pair of robot legs that will allow people to ditch their wheelchairs for hours at a time and get on with the business of living. Woo says that as he trains with the Ekso and gets better at using the walking sticks, he’ll be dreaming of that day.
Robert Woo: I look forward in the future that I will be able to walk with the crutches but also cook with it, do things! Walk in the park with my children.
Eliza Strickland: I’m Eliza Strickland.
Photo: Ekso Bionics
Brain-Computer Interface for Spinal Cord Injury
Susan Hassler: Every time you move your arm or even think about doing it, your brain generates electrical signals. Scientists are now trying to decode those signals and use them to move artificial limbs. A technology like this could make a world of difference to amputees or those who are paralyzed. And it has been tested for the first time on someone with a spinal cord injury. Prachi Patel visited the University of Pittsburgh Medical Center to find out more.
[ambient sound; wheelchair whirring; Tim Hemmes talking to girlfriend]
Prachi Patel: Tim Hemmes was 23 when he broke his spinal cord in a motorcycle accident. He was paralyzed from the neck down. That was eight years ago. Last fall, surgeons at the University of Pittsburgh Medical Center placed a small sensor on the surface of his brain. Four weeks later, Hemmes could move a robotic arm with his thoughts.
[ambient sound; robotic arm moving]
Prachi Patel: A video shows him concentrating intensely. The metal hand moves with erratic bursts and finally touches a researcher’s palm.
[ambient sound; “All right!” “There you go” “Yay!” “Nice!”]
Tim Hemmes: To have Wei standing there and to reach out to him, that was what I’ve been working for seven years. Whether it was robotic, whether it was metal and plastic—my mind, my thought process, put that there.
Prachi Patel: In 2008, the Pittsburgh team had shown that monkeys could feed themselves treats by controlling a robotic arm with their minds. Hemmes is the first human to have tried the technology. Michael Boninger, the lead physician on the research trial, shows me the sensor that was used to read Hemmes’s brain signals.
Michael Boninger: You can see there’s a bunch of tiny, like 1-millimeter silver spots. Those are the electrodes. And it’s through this small pad that’s the size of one of those designer postage stamps we’re able to record the electrical signals. The only thing we’re doing is recording the electrical signal that the brain normally produces when someone thinks.
Prachi Patel: People with spinal cord injuries can think about moving their arms or clenching a fist, but their brain signals can’t reach their arm. So the researchers direct those signals to a prosthetic arm through what’s called a brain-computer interface. Specialized software decodes the brain signals.
Michael Boninger: Right now, the electrode sits on the surface of the brain. The wires then come out, and we connect them to a computer. The computer then does the high-level analysis that says, “Okay, these electrical impulses mean that the subject wants to do this.”
Prachi Patel: Hemmes’s trial started with the researchers’ imaging his brain as he imagined moving his right arm. That helped them pinpoint which area of his brain was firing. Neurosurgeons placed electrodes on that area. Then the researchers recorded his brain signals as he watched a figure on the computer move its arm. Software analyzed the up and down spikes of those signals and learned what they looked like as Hemmes watched the arm move in a certain direction.
Michael Boninger: The way we figure out the code is by having the subject watch the arm move. We see this electrical activity; that’s the code. And then we say, “Okay, now imagine the arm’s moving,” and we use that same code to drive the arm to move.
Prachi Patel: Once the computer had learned Hemmes’ brain signals, it was his turn to train. Six days a week for four weeks, Hemmes practiced working with the brain-computer interface. He first tried to move a red ball on a computer screen to the left, right, up, or down.
[audio from two-dimensional computer training video]
Michael Boninger: Tim was able to generate a really strong signal when he thought about flexing his wrist or extending his wrist. We linked that thought to a specific movement of the cursor to a specific spot in space. So Tim knew that whenever he thought about flexing his wrist, the ball would move to the right.
Prachi Patel: The thought of bending his elbow or flexing his thumb generated other signals. The researchers linked those to different cursor movements. Tim Hemmes progressed to moving the ball diagonally and then on a three-dimensional screen.
[whirring sounds; “bing” sound]
Prachi Patel: Finally, he went on to the robotic arm, controlling it to reach out and touch targets arranged on a panel.
Prachi Patel: Slowly but surely, Hemmes could take the arm where he wanted it to go. A dramatic video shows him touching his girlfriend’s hand.
[ambient sound; “aww”; “baby”]
Tim Hemmes: [laughs] Yeah, the feeling of that was, obviously the adventure isn’t over yet. We’ve still got lots of stuff to do here, but all my hard work for the last seven years was put into that one moment, and it wasn’t my arm, but I was able to do it, and that was really touching to me.
Prachi Patel: The Pittsburgh research team wants to test the technology on at least five more patients. They also plan to make it wireless. Neurobiologist Andrew Schwartz, who has been working on this technology for years, says moving a prosthetic arm is just the beginning.
Andrew Schwartz: And the next step, then, is to put sensors on that arm—for instance, tactile sensors on the fingertips—so when the hand encounters an object, it can feel that object and convey that back to the brain and stimulate [the] sensory region of the cortex so [the] subject has some sort of idea what they are touching.
Prachi Patel: It might also be possible to use the brain-computer interface to stimulate muscle fibers so that patients could use their own arms. But that’ll come in the future. For now, Hemmes says he did his part in furthering the technology and looks forward to the day 5 or 10 years from now when it will help him.
Tim Hemmes: Seeing what I was able to do, I believe in this wholeheartedly. And I believe this is one avenue for the future for spinal cord injury. And reaching out and grabbing a door, you know, being able to grasp a drink instead of asking for something...I mean, I’m solely dependent on everything, you know. If I have a runny nose, to wipe my nose, you know, to grab a drink, to open a door—anything. What would this type of technology do? It would completely change my world. I don’t—I mean in every aspect of it, it would completely change my world for the positive.
Prachi Patel: This is Prachi Patel.
Artificial Materials to Repair Damaged Nerves and Disappear
Susan Hassler: Burns, cuts, and surgeries can harm nerves, leaving people without muscle control. In severe injuries, nerves don’t regrow on their own. Scientists in Austin, Texas, are making artificial materials that will repair damaged nerves and disappear when their job’s done. Phil Ross has more.
[door click and slam; footsteps]
Craig Milroy: We’ve made films, and—sorry, these have been cut up a little bit for analysis, but—these are conductive, but they’re also elastic.
Phil Ross: In a large, brightly lit laboratory at the University of Texas in Austin, Craig Milroy holds up small pieces of a black, rubbery film.
Craig Milroy: And these—so, you can stretch them. And this…
Phil Ross: Milroy is a chemical engineering graduate student. He’s trying to blend flexible plastics with plastics that conduct electricity.
Craig Milroy: The materials don’t like to be together, okay? And so, part of the challenge is to get just chemically dissimilar stuff to blend together and to be happy together.
Phil Ross: Now he has to make them safe for use in people. He wants to create a material that would electrically stimulate nerves to grow faster. These engineers believe it’s a way to help heal injured nerves.
Christine Schmidt: We’re developing a number of different biomaterials that could be used to regenerate nerve tissue.
Phil Ross: Biomedical engineer Christine Schmidt is leading the nerve regeneration efforts. She wants to find a material that would provide all the right conditions for injured nerves to heal and grow and then vanish once the nerves are healed.
[voices in laboratory]
Phil Ross: When nerves are severed, nerve fibers, or axons, cannot grow across large gaps between the two ends. So surgeons have to transplant nerves from another part of the body. And for spinal cord injuries, there’s nothing they can do.
Christine Schmidt: So the materials that we’re working with would basically be implanted at those sites of injury so the axons have a substrate, a substance, along which to migrate and to regenerate.
Phil Ross: Normally, nerves grow by attaching to proteins and sugars in body tissue. Chemical and electrical signals guide this growth. Creating artificial materials that provide nerves with all those growing conditions is challenging, Schmidt says.
Christine Schmidt: What are the correct signals we need to put into these grafts? What size pathways do we need? What pathways are they going to want to follow? Those are all questions we’re trying to address right now.
Phil Ross: The researchers have learned a lot from cells studied in a glass dish. For instance, certain proteins trigger nerve growth. So the researchers implant their artificial materials with cells that secrete those proteins. One of the materials they’re working with is that stretchy plastic Milroy showed us. Another is a natural, Jello-like compound that’s used in arthritis injections. Graduate student Eric Spivey uses a laser beam to draw lines inside gobs of this gel.
Eric Spivey: We use pulse lasers to generate what’s called multiphoton excitation. All that means is it allows us to create a lot of energy at the focal point of the laser that we can use to do specific kinds of chemistry.
[ambient talk and humming]
Phil Ross: The gel is soaked with liquid protein that becomes hard when it’s heated, just like an egg. Looking through a microscope, Spivey moves the tiny red laser point around inside the gel. Soon he’s made an intricate pattern of proteins that look like spaghetti strands suspended inside the Jello.
Eric Spivey: And so, you can think about [it] like an Etch-a-Sketch, really. It’s pretty—pretty neat to see.
Phil Ross: The researchers have already found that nerve cells grow along those protein strands. And they’ve come up with some tricks to control the growth direction. With their lab setup, though, they can only make millimeters of the gel. They need to make centimeters’ worth for animal implants. The group is also working on a gel that could be injected into the spinal cord to repair nerves.
Sydney Geissler: So I can show you a gel I just made a few minutes ago.
Phil Ross: Graduate student Sydney Geissler is in charge of this work.
Sydney Geissler: And then this one has collagen. This one has collagen and laminin.
Phil Ross: How hard or squishy the different gels are affects the development of stem cells in the spinal cord—specifically, what type of nerve cell they become, or, as Geissler calls it, differentiate into. She has found that in a softer gel, stem cells tend to become neurons.
Sydney Geissler: What I hope is that these gels—I will implant them with undifferentiated cells, and then these gels would direct the differentiation while they're inside of the spinal cord.
Phil Ross: The work is at an early stage. The researchers still face plenty of engineering challenges and extensive testing, in animals and outside. After that, they’ll need FDA [Food and Drug Administration] approval. But the implications, especially for spinal cord injury, could be huge. This is Phil Ross.
Photo: The Schmidt Lab/The University of Texas at Austin
Harvesting Blood From Limpets for a Cancer Vaccine
Susan Hassler: Sometimes new medical technology comes from very unexpected places. In Southern California, researchers have found a way to grow an unusual marine snail that may play a major role in the vaccines of the future. Lauren Sommer went to explore this unique laboratory site.
Lauren Sommer: When you think of cancer treatment, this probably isn’t the scene you’d imagine. But this rocky strip of land in Port Hueneme in Southern California is home to a unique medical facility.
Brandon Lincicum: So, what you’re seeing right now is—this is our primary production seawater system. Essentially, we pump nutrient-rich seawater right over here from the port.
Lauren Sommer: Brandon Lincicum is the aquaculture manager for Stellar Biotechnologies. We’re standing next to large tanks just a stone’s throw from the Pacific Ocean.
Brandon Lincicum: Take a look at some of these guys. Okay, so, this is what you’ve been waiting to see. This is Megathura crenulata right here, the giant keyhole limpet.
Lauren Sommer: Lincicum reaches into the tank and pulls out a round, purplish animal that looks like an abalone.
Brandon Lincicum: They do have a hard shell, but they have this mantle tissue that they can fold up over their shell so you know, when you touch these guys, they are almost soft. It’s almost...
Lauren Sommer: A little slimy.
Brandon Lincicum: A little slimy? Right? A little bit.
Lauren Sommer: The limpet he’s holding weighs almost a pound, but it takes years for them to grow this large.
Brandon Lincicum: So I’ll show you some of our up-and-coming limpets right here. So, if we take a look in this tank, these are our limpets, and these guys are fairly slow growing, but you can see them. These guys are about three and a half years old or so. We produce these guys from sperm and egg—microscopic sperm and egg. These guys are teeny tiny.
Lauren Sommer: This is the only place in the world where giant keyhole limpets are bred and grown. And there are thousands here, each with their own unique tracking number. The question is, why?
Frank Oakes: It pretty much is a nondescript member of the local California coastal environment but turns out to be really important when it comes to medical technology.
Lauren Sommer: Frank Oakes is the CEO of Stellar Biotechnologies. He says what’s special about giant keyhole limpets is their blood—or more specifically, something found in their blood called KLH.
Frank Oakes: Keyhole limpet hemocyanin. And then, hemocyanin is the protein from the blood, analogous to hemoglobin in humans.
Lauren Sommer: This unique blood protein, KLH, has been studied since the 1950s, and it’s played a major role in immune system research. But the keyhole limpet is only found in Southern California, which means there’s a limited supply.
Frank Oakes: It was harvested routinely for extraction of its blood, and with little regard to understanding the animal, its importance in the wild, or the perishability of the wild population.
Lauren Sommer: Oakes has a background in aquaculture, so he began studying how to breed limpets in captivity.
Frank Oakes: In the late 1990s, we started work on developing nonlethal extraction methods for the animal, so we can take the blood without killing them.
Lauren Sommer: Getting limpets to grow in captivity was no easy task. Oakes had to learn how to coax them into reproducing. He had to learn what conditions they grow best in. And because the limpets are part of medical research, there has to be strict quality control to prevent contamination. Today, thousands of limpets go through their entire life cycle in a controlled system, giving blood several times a year.
Frank Oakes: From a 50-animal lot, we get about a liter of serum. And from that liter of serum, we will typically produce about 20 grams of protein. And at retail value, that 20 grams of protein for us is approximately $100 000.
Lauren Sommer: Why would a blood protein be so valuable?
Herb Chow: Without it, a lot of the vaccines will not work.
Lauren Sommer: Herb Chow is a vice president at Stellar Biotechnologies. He says to understand why KLH is useful, you have to go back to the early days of vaccines. Medical researchers would take something harmful like a virus, kill it, and then inject it into your body. Your immune system would see the inactive virus and it would learn how to attack it.
Herb Chow: Except if you use the dead virus or that bacteria, it does accomplish that activation or stimulation, but it comes with a price. The price is some level of toxicities: People get sick because the toxin is still there.
Lauren Sommer: So researchers took viruses apart, pulling off the small chunks that your immune system could attack. They injected those smaller pieces as the vaccine, but there was a problem.
Herb Chow: Just too small. They don’t see it. So it becomes stealth to your immune system.
Lauren Sommer: And like a stealth plane, if your body doesn’t see it, it can’t learn to attack it. But attach those virus pieces to KLH, and it’s like attaching reflectors to the plane.
Herb Chow: By putting two together, all of a sudden the radar starts seeing it.
Lauren Sommer: And your immune system mounts an attack or starts making antibodies. KLH itself is neutral and doesn’t harm you. Chow says it’s being used in vaccine research for Alzheimer’s and autoimmune diseases. It’s also being used in cancer vaccine research.
Herb Chow: The problem with the cancer cells is a lot of the antigen that are expressed on the cancers is actually your own tissues. The body sees them: This is my own, I shouldn’t react to it.
Lauren Sommer: Cancer cells are, in essence, your own cells. So your immune system doesn’t see them as foreign invaders.
Herb Chow: And, as such, it fools your immune system to kind of ignore them and let them keep growing. And when the tumor mass gets to be a certain size, then your body no longer be able to handle it.
Lauren Sommer: So doctors use treatments like radiation and chemotherapy, which target all fast-growing cells in your body. But Chow says that’s why cancer vaccines have such promise.
Herb Chow: It’s something that it’s high on the radar screen because of the characteristics—that they can differentiate the normal cells from the tumor cells and be able to target the treatments to the tumors.
Lauren Sommer: Cancer vaccines could train your body to only attack the cancer cells. Chow says the challenge is finding something on cancer cells that would help your immune system differentiate them from your own cells.
Herb Chow: And there are differences, and it used to be we are looking at differences on the cell surface, and it seems like that difference is not big enough. There are some differences, now we’re going inside the cells, looking a lot—zillions of molecules inside the cells—and you find more differences.
Lauren Sommer: Today, most of the cancer vaccines that use KLH are still in the research phase or in clinical trials. But CEO Frank Oakes says the role of KLH is looking promising.
Frank Oakes: The long-term commercial demand for KLH looks very promising because it’s a key ingredient in a wide variety of drugs that are currently in clinical development.
Lauren Sommer: The challenge is that vaccines take decades to develop—and not all of them come to market.
Frank Oakes: Unfortunately, in this business, more drugs fail in clinical development than succeed.
Lauren Sommer: But Oakes says with the growth in cancer vaccine research, there’s a good chance that this mollusk from Southern California will eventually play a role in keeping us healthy. In Point Hueneme, I’m Lauren Sommer.
Photo: Lauren Sommer
A Revolutionary Cancer Treatment Device Inspired by the Mosquito
Susan Hassler: A team of engineers at Virginia Tech is developing a novel tool that could revolutionize the treatment of some cancers. It’s called a fiber-optic microneedle device, or FMD. It’s designed to deliver state-of-the-art treatments directly into a tumor. And it’s modeled on a creature you’re more likely to swat than celebrate. Mia Lobel has more.
Mia Lobel: When most people hear the tiny, high-pitched whine of a mosquito, they think of the fastest way to get rid of it. Virginia Tech mechanical engineer Christopher Rylander thinks of something entirely different.
Christopher Rylander: We know the mosquito can land on the human skin and insert their needle, their microneedle, several millimeters deep into skin. So we knew that the insertion of a very small-diameter needle was feasible based on nature’s example.
Mia Lobel: Rylander and his team were able to design a fiber-optic needle the same size and shape as a mosquito’s stinger. We’re talking about 40 microns here—less than the width of a human hair. And very sharp.
Christopher Rylander: So it can easily be inserted into the tissue with minimal surrounding tissue damage.
Mia Lobel: Less tissue damage, and potentially less pain, and quicker recovery times. But what’s unique about Rylander’s device is that it can do two things at once. It can inject fluids directly into a tumor—delivering things like conventional chemotherapy drugs or more-cutting-edge nanoparticles. It can also deliver light from powerful lasers. Two cancer-fighting treatments combined into one medical device to find and destroy unwanted tissue. This fiber-optic microneedle device—or FMD—is the basis for a whole series of experimental technologies that may one day change the way doctors treat cancer patients.
Christopher Rylander: So, collectively, what do we call this team, John?
John Robertson: The thing we call the team is Team Onco and the Cancer Engineers.
Mia Lobel: Dr. John Robertson is the director of the Center for Comparative Oncology at Virginia Tech’s vet school.
John Robertson: Everybody calls me Dr. Bob.
Mia Lobel: He’s a cancer survivor himself.
John Robertson: You can probably see the scar just under my ear here. So both my wife and I have—have dealt with neoplastic disease in the last couple of years. And boy, I really hate cancer.
Mia Lobel: Dr. Bob and his wife are both doing well now, but he knows that’s not the case for many cancer patients. He’s says the FMD could potentially go a long way toward treating some of the most aggressive cancers.
John Robertson: By the time that we see the more advanced forms of both bladder tumors and brain tumors in people, we’re past the point really where we’re going to do much to help them. The morbidity, mortality over the few years, three, four, five years, the amount of suffering, the things that happen to patients are just horrific... This device and the folks that are working with it and the things that we can do with it, the broad applications, are going to allow us to get at those advanced cases and offer these patients...some hope, some new ideas.
Mia Lobel: Common cancer therapies like chemo and radiation have a number of drawbacks. Chemotherapy is delivered directly into the bloodstream and is known for its devastating side effects. Plus, many chemotherapeutic drugs can’t cross the blood-brain barrier, making them ineffective in treating brain cancer. Radiation, at its best, is imprecise, and can create new cancers even as it treats existing ones. The Virginia Tech team works with lesser-known optical therapy treatments—using light to destroy cancerous tissue up close.
Christopher Rylander: Okay, now we’re walking down the hallway... I’ll swipe my access card, and it lets us into the laboratories.
Mia Lobel: Christopher Rylander shows me around the laboratory. It’s packed with optical equipment and a handful of grad students.
Christopher Rylander: You can see another student’s coming in about 11, 11 o’clock... They usually stay here hard at work until about 2 or 3 in the morning, and then they sleep it off and come in about 11 or maybe noon, just in time for lunch. Look, he’s blushing.
Mia Lobel: Off to the side of the main lab is a smaller room that houses some of the more sensitive equipment.
Christopher Rylander: So now we’re entering a room that has a few more optical components.
Mia Lobel: Two of Rylander’s grad students demonstrate the power of light to destroy tissue. A piece of pigskin smokes and crackles beneath the powerful beam.
Christopher Rylander: So many people think that lasers are very precise. But due to the phenomena of scattering of light and tissue, where the light is delivered actually becomes very blurry because the light does not stay confined to the region right at the point of delivery. The light will scatter out, analogous to how automobile headlights scatter in a foggy night.
Mia Lobel: The FMD is designed to control this scattering by delivering both light and light-absorbing nanoparticles at the same time. The nanoparticles are injected into the tumor, and the light is absorbed exactly where it needs to be.
Christopher Rylander: Okay. Now we’re heading out of our lab... We’re heading to my wife’s office, Nichole Rylander. She—she’s a collaborator on several of these projects, and her expertise is in nanomaterials and their use in treating cancer... Here she is.
Marissa Nichole Rylander: Hi. Hi, I’m Nichole Rylander. Nice to meet you.
Mia Lobel: Marissa Nichole Rylander is the director of the Tissue Engineering Nanotechnology and Cancer Research Lab. She and Christopher Rylander have been married since 2001.
Marissa Nichole Rylander: We met in freshman orientation, undergraduate freshman orientation at UT Austin in 2000—I’m sorry, in 1996. We were studying mechanical engineering at the time, but we both had significant interest in potentially pursuing medical school. But we just saw the huge reservoir of understanding in terms of engineering that we could apply to these biomedical problems that we found really exciting.
Mia Lobel: The couple has been working on the FMD project together since 2007.
Marissa Nichole Rylander: So we’re now entering the lab. So, I’m going to take you over to one of the graduates that are working on this project.
Kristen Zimmerman: My name’s Kristen Zimmerman... And I’m working on conjugating fluorescent nanoparticles to the surface of the carbon nanohorns.
Mia Lobel: Carbon nanohorns are flower-shaped nanoparticles with a relatively huge surface area. This is ideal for absorbing laser light and for transporting drugs to the targeted tumor cells.
Marissa Nichole Rylander: These particular particles that we look at, they’re on the order of kind of a spherical sort of Koosh ball shape. They’re a size and shape that cells like to bring into them... So it’s great for ferrying of drugs that might not otherwise cross the cell membrane.
Mia Lobel: Carbon nanohorns are also less toxic than other nanomaterials, which takes care of one major hurdle in clinical use of nanotechnology. But one main challenge remains: how to study the behavior of the particles in the highly complicated and unpredictable human body. So what they do is engineer body tissues in the lab to mimic the complex environment of a tumor.
Tobias Ecker: And this device—at this site we are basically trying to simulate the brain tissue.
Mia Lobel: A couple of students are looking at how the fiber-optic microneedle device could deliver nanoparticles in a real-life treatment situation. Grad student Tobias Ecker makes a small adjustment and plunges the FMD into a Jell-O–like substance called a brain phantom. He turns on a pump that slowly pushes blue dye into the synthetic tissue, creating a bloom of color that moves out and around the microneedle.
Tobias Ecker: And then we will take pictures in certain—like, certain time steps. And later on, we can use them at the computer, and we can basically look at different, like, concentrations and how the fluid disperses over time.
Mia Lobel: Brain cancer is one of the main targets for the fiber-optic microneedle device; it’s often one of the hardest cancers to treat.
Christopher Rylander: If you think of the roots on a weed in the grass, when you pull them out, they’re infiltrating into the dirt, and that’s how the brain tumor is in the brain.
Mia Lobel: So you can’t simply cut out the tumor. Using the FMD, surgeons could potentially highlight the cancerous tissue with light-absorbing nanoparticles, then destroy it with pinpoint accuracy.
Christopher Rylander: And we can do so perhaps painlessly, or at least minimally invasively, without creating too much bleeding and healthy tissue damage.
John Robertson: What has evolved here is the discipline of cancer engineering, where there’s been this cross-fertilization between cancer biologists and veterinarians and physicians and just a wonderful team of engineers that are able to bring together disciplines that normally wouldn’t talk to one another under a unifying theme, this cancer-engineering theme.
Mia Lobel: Center for Comparative Oncology director John Robertson says the team at Virginia Tech is unique in the nation, not just for its state-of-the-art technology but also for the interdisciplinary nature of what they do.
John Robertson: You know the nice thing about engineers? Okay. You—you got an idea, you got a problem, and you—you find a—you find a really bright series of engineers, a set of engineers, and they’re all sitting around, and [you] go, “Hey, guys, I need you to build something.” And they do. And then we test it, and then we say, “Well, we’d like it to change a little bit,” and then they change it. And then it gets better and better and better. We’re on a very rapid development path. It doesn’t take us—oh, let’s talk about it for three or four years. Our patients don’t wait three or four years. They die.
Mia Lobel: The team is on a fast track to get the fiber-optic microneedle device into clinical trials. As John Robertson says, cancer doesn’t wait. In Blacksburg, Va., I’m Mia Lobel.
Photo: Roger De Marfa/iStockphoto