Building Human Organs on a Chip
Susan Hassler: We’re going to start with the basic biological units of all known living organisms. Cells.
Phil Ross: When we talk about bionics, we typically talk about hardware that’s added to the human body to make it stronger or more capable. But Eliza Strickland is here to talk about an idea that goes in the other direction.
Eliza Strickland: Right. Here’s the idea: By taking living human cells from the body and adding them to external devices, scientists think they can make big improvements in medical research.
Susan Hassler: We’re still talking about the merging of humans and hardware, but that merging is taking place on gadgets in the lab?
Eliza Strickland: That’s right. And one particularly exciting example of this is called organ-on-a-chip technology. An organ on a chip is an attempt to mimic the essential functions of a human organ, like the heart or the lungs, on a chip of silicone rubber that’s smaller than your thumb.
Susan Hassler: And why do researchers want to make these miniature imitation organs?
Eliza Strickland: Well, they’re hoping that these chips can be used to develop new drugs. They say that testing new drugs on these organs on chips would be cheaper, faster, and less controversial than testing on animals. To learn more, I went to talk to the world’s foremost expert on this technology.
Don Ingber: I’m Don Ingber; I’m the founding director of the Wyss Institute for Biologically Inspired Engineering at Harvard University.
Eliza Strickland: I meet Ingber at the Wyss Institute’s headquarters in Boston, inside a glassy high-rise building. The institute is only three years old, and everything looks shiny and new. Ingber walks me through the labs and stops at a lab bench where some samples are displayed.
Don Ingber: Here what you see is a lung, a heart, a kidney, a bone marrow, a gut.
Eliza Strickland: But we aren’t looking at messy, fleshy organs oozing blood into jars. Instead, we’re staring at five small pieces of clear and flexible plastic with a few tiny lines etched into them. Several tubes are plugged into the chips to push air or a bloodlike fluid through them. These are very clean and simplified versions of our human organs.
Don Ingber: Yes, so this is the lung on a chip. It’s this crystal clear microdevice the size of a computer memory stick, so we can actually hold it although this mimics literally the mechanical breathing motions and flows and absorptions of the human lung.
Eliza Strickland: Tens of thousands of human cells are thriving on this chip. And they’re not growing in unorganized clumps, like they would in a petri dish. Instead, the chip replicates the basic structure of one of the lung’s 700 million air sacs, where blood flows through tiny capillaries and exchanges carbon dioxide for fresh oxygen.
Eliza Strickland: In this chip, a spongy and porous membrane is coated with the lung cells on one side, and air flows over these cells through a microscopic channel. The other side of the membrane is coated with the capillary cells found in our smallest blood vessels, and a fluid that mimics blood flows past those cells in another tiny channel.
Eliza Strickland: This allows researchers to watch biological processes happen in a simplified form, right there on the chip. So researchers can put a drug in the chip’s airway, for example, and watch to see how it’s absorbed into the blood.
Don Ingber: It is bringing it down to the essence.
Eliza Strickland: But there’s one more element necessary to mimic the human system. In our lungs, our air sacs expand and contract with each breath. So the lung on a chip has to expand and contract, too.
Don Ingber: This controls the breathing motions.
Eliza Strickland: In Ingber’s system, a precisely controlled pump applies suction to both sides of the rubbery chip.
Don Ingber: And the whole device is crystal clear, flexible silicone rubber, so when the suction is pulled, the device with the cells, the two layers of cells stretches, and then when it releases, they relax.
Eliza Strickland: These chips are fabricated using techniques learned from computer microchip manufacturing. That industry perfected ways of etching microscopic channels into silicon wafers to make patterns.
Don Ingber: It’s not like we’re forcing cells into microchips, but we’re using computer microchip fabrication to fabricate systems that meet our needs.
Eliza Strickland: Now that the researchers have built this functional model of a human lung, the next step is putting it to use. And that’s where the drug industry gets involved.
Don Ingber: The catchphrase that I’ve been told by pharmaceutical executives is we have to learn how to fail quickly and cheaply. But remember, a single drug, it can cost [US] $2 billion to take a single chemical all the way from discovery all the way through human clinical trials. This is a major, major decision.
Eliza Strickland: Ingber says that the current system of testing a drug in petri dishes and animals doesn’t predict very well whether it will actually work in human beings.
Don Ingber: They’ll do some work with cells in dishes, in fact, even human cells in dishes. But the problem is, when a cell is on a dish it loses most of the specialized properties it has in the body—it’s usually just proliferating, it’s not functional. And what they end up doing is really relying on animal studies to validate which drug to choose …
Eliza Strickland: And Ingber says that animal studies aren’t just controversial—they’re also ineffective.
Don Ingber: The problem is more often than not, what they predicted from the animal studies fails to predict what happens in humans, and they have these huge failures, and they’ve already spent hundreds of millions if not billions of dollars. And so that’s where there comes the phrase “We want to learn how to fail quickly and cheaply,” because they’d much rather say “This is a mistake” early in the process and then choose another drug.
Eliza Strickland: If drug companies can test a new drug on a chip that mimics the functions of a human lung, they can find out right away if the drug is toxic to human cells, and they can study how it’s absorbed into the bloodstream. The researchers can even introduce white blood cells into their chip systems to study how the immune system responds to the drug. And the lung on a chip is just the beginning.
Don Ingber: We’re working to many organs. We’ve made some breakthroughs in bone marrow on a chip, and kidney on a chip. We’ve targeted 10 different organs and the idea of linking all of them together in different orders and different ways.
Eliza Strickland: Ingber wants to link a whole series of chips together and to connect them with flowing fluids to mimic the way they’re connected in the human body. He’s essentially working towards making a human on a chip.
Don Ingber: It’s like taking a biology textbook diagram and bringing it to life.
Eliza Strickland: Creating life on a chip. The stuff of monster literature is alive and well and living on tiny chips in this Boston laboratory. I’m Eliza Strickland.
Photo: Wyss Institute
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Bionic Eye Implants Promise Vision for the Blind
Susan Hassler: Phil, do you ever wonder what it might feel like to actually be bionic?
Phil Ross: Sure, it’d be great! I mean, who wouldn’t want to have an arm as strong as a bulldozer or an eye that can zoom in and out?
Susan Hassler: I don’t know…maybe it wouldn’t be quite as fun as you think. I think I might feel a bit freakish. Like Edward Scissorhands or Frankenstein’s monster. But of course, that’s all science fiction. Our reporter Ariel Bleicher has a real-life tale about what it really means to become bionic.
Ariel Bleicher: Right. So let me just start by introducing you to someone.
Miikka Terho: Yeah, my name is Miikka Terho. I’m a native of Finland.
Ariel Bleicher: When you meet Miikka, he seems like just a regular guy. He’s in his late 40s, slender, athletic, blond hair, and he’s got these brilliant sea-blue eyes. But when he was a teenager, he found out he had a degenerative disease.
Miikka Terho: Yeah, it’s a disease called retinitis pigmentosa—RP, as they call it.
Ariel Bleicher: About a million and a half people have RP. They’re born with a genetic defect that causes cells in the retina—the tissue lining the back of the eye—to deteriorate over time. These cells—the photoreceptor cells—they detect patterns of light entering the eye. And they convert those patterns into electrical signals, which they pass on to their neighbor cells. Then those cells pass the signals on to their neighbors, and this relay chain goes all the way to the brain.
Susan Hassler: So if the photoreceptor cells stop working, the chain is broken.
Ariel Bleicher: Right. By the time Miikka was in his mid-30s…
Miikka Terho: Then I lost the central eyesight altogether.
Ariel Bleicher: He was blind for 15 years. Then one day he heard about a small experimental study led by an ophthalmologist and researcher at the University of Tübingen, in southern Germany.
Eberhart Zrenner: My name is Eberhart Zrenner. I run a clinic for hereditary retinal degeneration. I see patients with these diseases.
Ariel Bleicher: In the 1990s, Dr. Zrenner had this crazy idea.
Eberhart Zrenner: I thought about this concept: Why not replace natural photoreceptors with technical ones? They are everywhere, these chips – in the mobile phones and why not put it into an eye?
Ariel Bleicher: He put together a team of researchers, got investors, did experiments with rats and rabbits and pigs, eventually started a company. And the product that came out of all this effort was this…
Eberhart Zrenner: …very tiny, tenth-of-a-millimeter-thick little chip.
Ariel Bleicher: It’s about the size of a freckle.
Phil Ross: And this chip is surgically implanted into the eye—right where the dead photoreceptors are?
Ariel Bleicher: Yeah, that was the idea. It’s actually a really elegant design. The chip is made up of 1500 teeny-tiny electronic devices called photodiodes, each of which is paired with another tiny device called an electrode. And all these pairs of photodiodes and electrodes, they’re all laid out on the chip in a grid pattern. Basically, they act like little electronic pixels in a camera. So when light passes through the eye and falls on the chip, each of the 1500 photodiodes…
Eberhart Zrenner: … takes each point of the picture, translates it into a tiny little current.
Ariel Bleicher: Then the photodiode passes the current on to the electrode it’s paired up with. Then the electrode…
Eberhart Zrenner: … depending on the brightness of this particular spot, puts a current into the neighboring cell.
Ariel Bleicher: And the relay chain that was broken—it’s now fixed. Anyway, that was how things were supposed to happen.
Susan Hassler: Supposed to happen?
Phil Ross: Let me guess. It didn’t work.
Ariel Bleicher: It didn’t work. At least not the way Dr. Zrenner had hoped. In 2005, he started a small pilot study with 11 patients. And the first 10 patients, they couldn’t see much at all. Some of them could tell whether a line on a computer screen was horizontal or vertical. But that was about it.
Eberhart Zrenner: We didn’t know at the time whether we will have success ever. But there was one patient, the last patient—essentially, Miikka.
Ariel Bleicher: The results from the first 10 patients were so poor that Dr. Zrenner and his research team, they decided to do something a little different with Miikka. They told the surgeon to place the chip right in the center of Miikka’s eye, under a structure called the fovea, which in sighted people is responsible for producing really sharp, detailed images—like the text on a computer screen or the features on someone’s face. The researchers had avoided the fovea before because the tissue is especially delicate, and they knew the chip wouldn’t be able to produce perfectly sharp images anyway. But this was their last patient, maybe their last chance, and they figured it was worth a try.
Ariel Bleicher: When Miikka woke up from the operation, the first thing he remembers was, he was groggy and he had a headache. He looked like he’d been punched in the face. The skin around his left eye, where the chip had been implanted…
Miikka Terho: …it was like in all rainbow colors: yellow, green, purple.
Ariel Bleicher: The only evidence of his new bionic self was a slender wire power cable, with a plug at the end, poking out from the skin behind his ear. One of the researchers attached a control box with a battery to that cable, flipped a switch…
Miikka Terho: …and then I was asked like do I get any kind of visual sensations and I said yes. There was a flash of lights, many flashes of lights.
Ariel Bleicher: At first, he had no idea what he was looking at. He just knew he was seeing.
Miikka Terho: But then minute by minute, hour by hour, then everything started making more sense.
Ariel Bleicher: He learned to read simple letters again: Ls, Ts, Cs, Os. And recognize objects…
Miikka Terho: Fork, spoon, knife blade, mugs, cups…
Ariel Bleicher: He even took a vision test and scored just above the cutoff for being legally blind.
Phil Ross: Wow! So after 15 years of being blind, he can see again!
Ariel Bleicher: Not exactly. Three months after Miikka got the chip, a surgeon went back in and took it out.
Susan Hassler: They removed the chip that had given him sight?
Phil Ross: Why?!
Ariel Bleicher: Protocol. Remember, this was a pilot study—to show it’s worth doing a big clinical trial. It was the first time the chip was going to be implanted in humans, and the researchers wanted to take as few risks as possible—avoid infections and things like that. So they left the chip in just long enough to test it, and then took it back out.
Susan Hassler: So now that Miikka’s gotten a taste of this new bionic vision, does he miss it?
Miikka Terho: Oh yeah. Like I said of course, naturally. It would be nice to get the chip back or even get the eyesight back. But also I understand that whatever, if I ever get any kind of a central eyesight back permanently, it’s not normal seeing. I cannot just go to the beach and look at the babes. It’s not that good. I may go there and I see the shapes of those babes [laughing], but I cannot really identify them. So it’s not that normal seeing ’cause it’s an artificial form of seeing anyway. But then it will be a hell of a lot better than nothing.
Ariel Bleicher: It’s still evolving—and improving. I visited the company in Tübingen, Germany, that’s making the chips—it’s called Retina Implant. They’re currently in the middle of a clinical trial, and they expect to get approval to sell the device in Europe by the end of the year. So far, they’ve tested the newest version in 22 more patients, and some of those patients can see just as well as—or in a few cases, better—than Miikka.
Phil Ross: And surely someone someday will make a bionic retina as good as a natural one.
Susan Hassler: Or better!
Ariel Bleicher: Well, it turns out that’s still a pretty big dream. A natural human retina has about 115 million photoreceptors, whereas the chip has just 15 hundred electronic ones. So the technology definitely has a ways to go. But I did ask the CEO of Retina Implant—his name’s Walter Wrobel—I asked him what he thinks might be possible in the future.
Walter Wrobel: [sigh] I don’t know. I really don’t know.
Ariel Bleicher: He says probablyyou could improve the chip’s picture quality by finding a way to squeeze in more electrodes and photodiodes. You could also maybe widen the window through which a patient sees—his visual field—by implanting several chips in a row. But then Wrobel, very casually, he said something that totally surprised me.
Walter Wrobel: You can also think about being able to recognize infrared light…
Phil Ross: Wait, did he just say an electronic retina could recognize infrared light?
Walter Wrobel: …infrared radiation, which is very close to red but not visible anymore.
Ariel Bleicher: It’s just outside the wavelengths of light that you and I can see.
Susan Hassler: So he’s saying that it’s possible for people with this chip to see things that even sighted people can’t see?
Walter Wrobel: Yeah.
Ariel Bleicher: Crazy, right? Wrobel told me that one day, out of the blue, one of the study patients suddenly blurted out to two doctors in the testing room…
Walter Wrobel: “Oh, you have different coats. One coat is bright and the other one is dark.” And they were astonished because both of them had dark coats.
Ariel Bleicher: But the patient insisted…
Walter Wrobel: He said, “No, no—one is bright and the other one is dark.” Hmph.
Ariel Bleicher: So the researchers looked at the coats through a night vision scope, which can detect infrared light. And sure enough…
Walter Wrobel: …and it really turned out that in infrared, one of the coats looked bright—made from plastic, looking bright. And the other one was cotton or wool and was dark. So he really could see this infrared light.
Phil Ross: Wow. So what’s stopping the company from making a chip that lets people see, say, ultraviolet light, like butterflies do?
Ariel Bleicher: Well…nothing! But Wrobel says that’s not the point.
Walter Wrobel: There are some science fiction authors and so on who are dreaming about that. We are not dreaming; we are realizing our devices.
Ariel Bleicher: Miikka has a similar grounded attitude toward the whole experience. He says the chip didn’t make him feel like a superhero, and it didn’t make him feel like a freak either. He was just happy to take part in the pursuit of something important and good—something that could help a lot of people. Which, if you think about it, is all we can ever really ask from technology—that it help make us better versions of the selves we already are. I’m Ariel Bleicher.
Photo: Retina Implant
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Turning Tobacco Plants Into Vaccine Factories
Susan Hassler: We’re going to move on to a different kind of bionics now: from bionic body parts to another kind of biotechnology based on natural processes.
Phil Ross: It’s happening at the University of California, Davis.
Susan Hassler: We’ve been promising to tell you about researchers hijacking tobacco plants. Well, this is it.
Phil Ross: They’re using tobacco plants to produce compounds that are otherwise really expensive and hard to make. Vaccines.
Susan Hassler: Bottom line: They want to be able to develop vaccines more quickly and cheaply.
Phil Ross: Here we go, to the UC Davis laboratory where chemical engineer Karen McDonald works.
Karen McDonald: And what I’ll do is I’ll first take the top off of the vacuum chamber. It’s a chamber that’s about, oh, about a foot in diameter and maybe 18 inches high.
Susan Hassler: She takes a small tobacco plant, cut at the base, and places it upside down into a clear solution. She replaces the top of the vacuum chamber and then flips a switch.
Karen McDonald: And as the vacuum increases, what we’ll see is that the air that’s inside the leaves that are submerged in the liquid will actually start coming out of the leaf. And at the surface of the leaf, these bubbles will be generated, and then those bubbles will rise up to the air interface. It takes a few minutes to reach the vacuum level.
Phil Ross: This is a process called vacuum agroinfiltration, and it’s used to inject new DNA instructions into the cells of the plant. These instructions tell the plant to produce a protein that it wouldn’t produce naturally—for example, a vaccine for the common flu.
Karen McDonald: The main thing that inspired me to pursue this project was the realization, probably primarily in 2009 when the H1N1 pandemic arose, that the current manufacturing technologies to make vaccines aren’t fast enough to respond to a new pandemic. So what we found over the last few years is that plants, and particularly tobacco, make very efficient biofactories to make vaccines very quickly. And the technology that we use is one in which we can basically go from the genetic instructions for the vaccine to making the vaccine in several weeks.
Susan Hassler: Traditional egg-based vaccine production generally takes a few months and is quite costly, about ten to fifteen dollars a dose. McDonald’s process could dramatically speed this up and lower this cost to less than a dollar per dose, potentially revolutionizing the industry.
Karen McDonald: And so basically we’re using the biosynthetic machinery of the cells within the leaf, the plant cells, to make our product for us. And the—the advantages are that those cells have been grown using photosynthesis, one of the most efficient—energy-efficient—processes around.
Phil Ross: Right now, McDonald’s vacuum infiltration process can yield 1 to 10 doses per plant. But with a bit of tweaking, she expects to be able to get up to 100 doses. All using a plant that’s naturally suited to this kind of work.
Karen McDonald: Tobacco plants are a good host to make vaccines for a couple of reasons. One is that tobacco’s a nonfood, nonfeed crop, so you’re not competing with other uses of the plant. It’s a big, leafy, high-biomass plant, and for our applications we need leaves, a lot of green leafy tissue, so in that aspect, tobacco’s a good host. And also tobacco farmers are looking for alternative uses of tobacco other than smoking, and this is a efficient use of it to make a high-value product.
Susan Hassler: That’s products plural, actually. Her method isn’t limited to flu vaccines.
Karen McDonald: Yeah, this type of production could be used to produce basically any type of recombinant protein. And that would include things like monoclonal antibodies, industrial enzymes, biodefense agents, human blood proteins, biopolymers.
Phil Ross: A whole host of compounds that have traditionally been hard to produce in a scalable way. McDonald’s process essentially turns these tobacco plants into mini biofactories, pumping out proteins faster, cheaper, and more efficiently than current manufacturing processes.
Karen McDonald: So now we’re about 15 inches of mercury, and I’ll go ahead and release the vacuum. And at that point you’ll see the leaves turning from a light green to a very dark green. [loud noise] And then we’ll take the top off, take the top off the vacuum chamber. And you can take the leaves out and you can see visually the dark areas of the leaf where the solution has infiltrated the tissue.
Susan Hassler: She lets the plant dry for a few minutes and then places the leaves into a humidified box.
Karen McDonald: And we just store it in the dark for, like I say, five to seven days and let, let the plant cells do their thing.
Phil Ross: All you need are the right genetic instructions.
Karen McDonald: We’re hoping that our work helps to basically catalyze this new industry in which plants are used to make high-value, very important protein products. And so that’s—we’re hoping to bring more attention to this strategy as a biomanufacturing strategy and hopefully lower the cost of therapeutics and increase the speed with which new molecules can be produced.
Susan Hassler: They’re pretty close. But McDonald and her team still need to figure out one key step.
Karen McDonald: So my perspective as an engineer is always one in which everything we do in the lab we look at from the perspective of, “Is this process step scalable? Or are there constraints that would limit the scalability of the process?” Because we recognize that even though you could make a vaccine in a very small scale in the lab, can you do this in a large scale where you need to make millions of doses of the vaccine? And so sort of an attention to each of the steps and how scalable those steps are is an important aspect that I think engineers bring to the team.
Phil Ross: Scalability of McDonald’s process—the fact that it’s easily expanded or upgraded as needed—means larger and more efficient vacuum infiltration pumps and a huge and readily available crop of tobacco plants.
Susan Hassler: Once the vaccine has been produced, you have to get it out of the leaf. Which in McDonald’s case means grinding it and separating it from all the other proteins and plant parts that you don’t need.
Phil Ross: That can be a messy and inefficient process; you essentially destroy your manufacturing plant every time you harvest.
Susan Hassler: But we’ll tell you in a moment how scientists get around that. Stay with us.
Photo: Gregory Urquiaga/UC Davis
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Tobacco Plants: Efficient Protein Makers?
Susan Hassler: We promised to tell you how researchers are turning tobacco plants into biofactories without destroying the plants.
Phil Ross: The workaround involves doing something tobacco plants do all on their own.
Susan Hassler: Here’s Mia Lobel with the story.
Mia Lobel: So where are we headed?
Bob Morrow: Going down into the basement where most of our laboratories are located.
Mia Lobel: Bob Morrow leads me down a cement staircase at Orbital Technologies in Madison, Wisconsin. There’s a series of heavy doors in the dim hallway. He opens one, and I’m hit with a blast of hot air.
Bob Morrow: This is the room that Ryan’s using right now for his plants.
Mia Lobel: It’s a space about the size of a small dormitory, packed with 15 or 20 tobacco plants of various sizes, broad leaves swaying in the forced air. It’s about 75 degrees in here—and humid.
Ryan Shepherd: The room itself, we love it, because—I mean, it’s a secured environment, and the plants grow better here than, than any greenhouse I’ve ever seen.
Mia Lobel: That’s Ryan Shepherd, cofounder of the biotech start-up PhylloTech. His lab is just a few miles up the road at the university research park. But he keeps his plants here, where Bob Morrow can control the temperature and humidity, carbon dioxide levels, and light to create an optimal growing environment.
Ryan Shepherd: So if you, I mean, if you look at some of these tobacco plants—I mean, the leaves are huge. I mean they have, you know, a couple of feet in length. And you know, you can imagine the entire surface area is covered with trichome glands. That’s a large amount of productive space that we can now harness for protein production.
Mia Lobel: Trichomes are the little hairs you see on the surface of tomato and potato plants, sunflowers, and tobacco leaves. They secrete compounds that protect the plant from predators, parasites, and fungus. And they’re the key to the process Shepherd has been able to harness to turn these tobacco plants into biofactories for valuable and hard-to-produce compounds.
Ryan Shepherd: Most current efforts at using plants to make heterologous proteins—the proteins are typically made in leaf interiors, and so then they have to be collected in some manner. And that typically requires grinding up leaves and then trying to purify the protein.
Mia Lobel: Tobacco plant proteins can be collected by simply washing them from the leaf’s surface. This opens the door for countless potential opportunities in biomanufacturing.
Ryan Shepherd: All of this stemmed from a basic fundamental observation in plant pathology: the secretion of these native proteins. And you know, once we determined how these native proteins arrived at the leaf surface and what they did, we can now ask the questions to where exactly can we go with this. You know, what, what other applications can we approach?
Mia Lobel: If Shepherd could genetically alter the plants’ DNA to produce other proteins, he could potentially use tobacco plants as biofactories to secrete whatever protein he wanted. His first target is the silk of the black widow spider.
Cheryl Hayashi: Latrodectus hesperus; it’s a native species to Southern California here. I find them very charming, actually. [Laughs]
Mia Lobel: Cheryl Hayashi is a biologist at UC Riverside. She’s been working with spiders for more than 20 years.
Cheryl Hayashi: Spider silk has captured the attention of a lot of, you know, engineers, biologists, industrialists because of its wonderful combination of mechanical properties. So it’s strong. A lot of other materials are strong, but it’s also stretchy. And it’s this combination of being strong and stretchy that really, really, really make them different from most other materials that people use, you know, for building things.
Mia Lobel: The applications for this light and flexible yet superstrong material are endless: high-performance textiles; biomedical applications like high-tech bandages; artificial joints, tendons, and ligaments; electronic devices…not to mention high-fashion clothing items.
Cheryl Hayashi: Another really appealing aspect to spider silk is that it’s protein-based. So it’s not a petroleum-based material such as nylon, for instance. And being protein-based, it means it can be a green technology.
Mia Lobel: But collecting spider silk for broad use is impractical, to say the least. A few years ago, an international group of artists displayed a 13-foot spider silk cape. It took seven years and more than a million spiders to complete.
Cheryl Hayashi: So, you know, I get calls pretty frequently from people that say they have a good idea for how to use spider silk and, you know, could I send them a hundred pounds of it. And that’s, you know, pretty darned prohibitive. You know, I can’t have undergraduates, you know, having that many silking sessions with spiders in my lab. It’s just—we just can’t do it. And that’s just not feasible.
Mia Lobel: But if Shepherd could successfully produce spider silk proteins in his tobacco plants, he could potentially scale that process to create enough material for all kinds of applications. In 2010, Hayashi sent Shepherd his first sample of spider silk DNA. Shepherd inserted this DNA into the tobacco genome and let the plants grow with the new genetic instructions. And it worked. The tobacco plants secreted the spider silk protein right to the surface of the leaves, where it could be collected, studied, and, they hope, one day soon, spun back into a fully functional strand of silk.
Cheryl Hayashi: You know, I want to see a big bucket of each of those kinds of silk proteins, and I want to—my next thing I want to see is, you know, fibers made from those big buckets of plant-produced silk proteins. And I think, you know, once we have that kind of material, really, I think the sky’s going to be the limit in terms of, you know, what we and other people would be able to do with that material.
Mia Lobel: Even more exciting is the possibility this raises for other proteins—any large protein, really: antibiotics, enzymes, antibodies—all produced faster, cheaper, and more efficiently than they are now.
Ryan Shepherd: Now, our innovation, I believe, is that by targeting the production to trichome glands we are able to not only utilize the plant to produce the protein but also purify it so that we don’t have to grind up the leaf and destroy the plant to recover the protein. And we don’t have to spend, you know, a lot of time, money, and resources trying to extract the target protein from everything else that exists within the plant. So really the hardest part of this is the initial generation of the plant. But once you achieve that and collect seeds, then, yeah, you basically have a system with unlimited growth.
Mia Lobel: Ryan Shepherd says this could transform the way people look at plants.
Ryan Shepherd: I’m hoping that, that our work with trichome bioproduction will enhance people’s opinions of plants as bioproduction platforms. And that by targeting proteins to the glands—essentially using the plant to both produce and purify the protein—that we will be able to make a cost-effective system for protein production.
Mia Lobel: The success of this process could have far-reaching effects.
Ryan Shepherd: So I am a plant scientist, a plant pathologist. I, I very much like the idea that we’re taking a basic fundamental discovery in plant pathology—the idea that plants secrete proteins to their leaf surfaces to provide resistance against pathogens. It’s very exciting to me and invigorating that we can take that discovery now and utilize it for a truly applied purpose: the production of other proteins. And so I think the broader implications are that plants using our technology will hopefully become a viable production platform for many other targets in addition to spider silk and the things that we’re working with currently. And I think once that is attained, plants could be the go-to source for protein production.
Mia Lobel: Shepherd says he hopes to have his tobacco plant biofactory fully operational in the next three to five years. I’m Mia Lobel.
Photo: Mia Lobel
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Skinlike Walls Could Slash a Building’s Energy Use
SUSAN: We began this hour with some of the smallest-scaled bionic technologies. And we’ll end by reporting on a technology that will surround you—the Living Wall.
PHIL: It copies the way your skin works to regulate your body temperature.
SUSAN: Laurie Howell went out to explore the Living Wall.
Laurie Howell: We begin in the Engineering Center at the University of Colorado. It’s a picturesque campus at the base of the Rocky Mountain foothills. This is where John Zhai, an architectural engineering professor, leads a multidisciplinary team of engineers and architects on a creative venture of a lifetime. They’re designing what they call a “living wall.”
John Zhai: Traditional building designs just want to block the heat. “Hey, we don’t want to heat—don’t let the heat in.” We say, “Okay. Let the heat in, but we’re going to deliver this heat to where we need it.”
John Zhai: Okay. So, this is our building system lab. [unintelligible] So, come on in…
Laurie Howell: John Zhai calls the living wall the “skin of the building” because it would autoregulate the temperature of a building, just as skin helps regulate body temperature.
John Zhai: The veins underneath the skin can take the heat from the surface to the body and also can have a fat that’s kind of insulation. So this automatic system is natural in our body. So if we think of the whole building as a body, so the envelope of that is skin.
Laurie Howell: It’s like a human vascular system of capillaries, veins, and arteries: Water is collected at each floor through small tubes and pipes within the living wall, controlled through a computerized brain or building automation system. The hot water is redistributed throughout the building for heating, domestic hot water, or adding heat into the shaded living walls to augment the chimney effect for cooling. The entire system works on a basic law of thermodynamics. The living walls move energy from hot to cold very rapidly and efficiently, whether collecting or distributing heat through water or air.
John Zhai: So the envelope of that is skin. So, can we do something similar or mimic to this natural body systems, which has the fat insulation layers, have all these veins, those blood flow, the air flow, all the stuff, and then very likely we can have a building envelope that can adapt to the environment. So whatever environment is changing, the core body, body inside temperature is always constant. So if we can achieve that same thing, that would be perfect.
Laurie Howell: Zhai says the living wall system could slash energy use by—get this—75 percent. And energy use decreases 75 percent not by improving heating and cooling systems but by eliminating them altogether. No more boilers or chillers to create that comfortable room temperature. The living wall system would use passive heating and cooling: working with the outside temperature instead of against it.
Zhai’s fellow CU professor Fred Andreas is the lead architect on the team putting this million-dollar prototype together.
Fred Andreas: There’s no reason, other than business as usual, that we heat and cool and light our buildings the way we have: as hermetically sealed units that are disconnected from the environment. So the idea of the living wall is to turn the skin of the building into a living skin, copying essentially biologic processes and so trying to autoregulate heat and cooling and ventilation and light through the skin of the building and supplant the huge HVAC systems, heating, ventilation, air-conditioning systems inside of any building and then using natural daylight as much as possible.
Laurie Howell: The outside layer will use current smart glass technology which can block or tune the sun’s rays and control how heat and light enter the wall. The next layer of the living wall is just open space for collecting and distributing passive heating and cooling. And the bottom of the wall, there will be cool water coming in from a source, such as a river, or a lake, or the ocean, or an underground aquifer. And the top of the wall will be hot from baking in the sun. Now think about how a chimney works, and that’s what happens here: The cool-hot temperature difference produces an updraft, and that updraft passively forces hot air up, up inside the multilayered walls, drawing cool air through the building and producing natural ventilation. The hotter the air, the faster it rises. So as crazy as it is to imagine, for this passive cooling design, the hotter the wall, the better!
John Zhai: That’s a testing room we have here which can test all the building systems, the walls, systems. So this is one of the chambers. Watch the steps.
Laurie Howell: We’re walking along an HVAC system which stretches for roughly 40 feet. There are two rooms which can be made any temperature. This will be where the team installs and tests its first prototype.
John Zhai: So, you see all these air systems. We have water panels here. We can, this can provide radiation. We can simulate solar radiation so we can, you know, mimic the outside environment, so we don’t have to go outside to do the real test, cause there’s challenging where the real environmental test is.
Laurie Howell: The team envisions one day creating living wall kits for retrofitting buildings, possibly even homes. But right now, they’re focused on overcoming some puzzling design issues. Their biggest challenge is a layer in the living wall that will be made with something called hydrogels. Hydrogels are chemical compounds, or polymers, that absorb or release liquids depending on temperature. They’re used in products, such as diapers, and for a variety of purposes, such as tissue engineering. And they are key to making the living wall work because when the temperature changes, hydrogels embedded in the wall begin pumping water. Depending on the temperatures outside and inside the living wall, the hydrogels pump hot or cold water from one side of the wall to the other, cooling or heating the building. The big challenge for these researchers right now is how to contain the hydrogels within the living wall.
Fred Andreas: So that’s the challenge is, how do we get a plastic collection panel that maximizes heat collection at its best and move that heat through these flexible gels into the depth of the panel, and how do we get those flexible gels into the panel in manufacturing? That’s our challenge right now.
John Zhai: Right. That’s why we cannot use traditional concrete or wood. Right? We’ll have to use a polymer material that’s [a] porous medium so that these kinds of materials can be embedded or attached somewhere in the polymer, those bubbles, so that makes a whole piece of a wall.
Fred Andreas: And here’s the other challenge is, it can’t be glass because glass, when it’s formed, is so hot that it would destroy these hydrogels. So we have to figure a way to get these hydrogels infused into this panel at a relatively low temperature.
Laurie Howell: This is not just another greener building design, this is a change in the way we’ll design the buildings of the future.
Fred Andreas: Typical systems and typical approaches with the same kind of HVAC systems, although they’re very high efficiency and they’re very high technology, they’re still using the same assumptions that we’ve used throughout the 20th century. And this fundamentally changes it, basically moves away from the idea of interior-conditioned buildings to passively controlled buildings.
Laurie Howell: Yeah, truly a game changer.
Fred Andreas: Game changer.
Laurie Howell: And that’s why it’s captured the imagination of the next generation of building designers. Grad students Tamzida Khan and Scott Rank are excited about what’s on the horizon for smart building design.
Scott Rank: You know, pretty soon there shouldn’t be green architecture. It should just be architecture and that should be in all of it, integrated into it. So, I think, yeah, we’ve come a long way, but I think it definitely has a lot further to go as well.
Tamzida Khan: If we don’t take risk, then we will not move forward, and I think it’s really important for us to take risks.
Fred Andreas: I keep saying to my students I fundamentally believe that they’ll be looking at this period of time right now, this change to the 21st century, that they’ll be looking back at this in 1000 years as the Renaissance, equivalent to the artistic and cultural renaissance that happened previously. I think that this is an architectural and engineering renaissance that we’re experiencing right now at the early part of the third millennium.
Fred Andreas: I think the sky is the limit.
Laurie Howell: In the early part of the third millennium, reporting on what’s possibly an architectural and engineering renaissance, I’m Laurie Howell.
Susan Hassler: Living walls, like our body’s own layers of skin.
Phil Ross: Intriguing concept! I like it.
Susan Hassler: And what a payoff! By eliminating heating and cooling systems, the energy costs drop 75 percent.
Phil Ross: Working with the outside temperature instead of against. it. More to watch for in our bionic future.
Susan Hassler: You’ve been listening to “Becoming Bionic,” a coproduction of IEEE Spectrum magazine and the Directorate for Engineering of the National Science Foundation.
Phil Ross: The directorate supports people whose discoveries and inventions make our lives more productive, sustainable, and enjoyable.
Susan Hassler: For transcripts of this program, and expanded stories, check out the IEEE Spectrum website: Spectrum.ieee.org.
Phil Ross: You’ll find many other engineering features at the website for the National Science Foundation: NSF.gov.
Susan Hassler: Our thanks to Cliff Braverman, Cecile Gonzalez, Valerie Thompson, John Wassel, Prachi Patel, Nancy Hantman, Ramona Gordon, and Paul Ruest at the Argot Studios.
Susan Hassler: Our technical producer is Dennis Foley. Our executive producer is Sharon Basco.
Phil Ross: I’m Phil Ross.
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