Synthetic biology and living processors

Image from: SBC@MIT

As crazy and sci-fi as it might seem to think of building a computer using cellular components, it was even more shocking to me to learn that the term, “synthetic biology” has a history that goes all the way back to 1910. In fact,  in 1974, Polish geneticist Wacław Szybalski used the term to examine the idea of using molecular biology in a synthetic manner to “devise new control elements” in a modular manner for creating new genomes, new organisms, etc… BRILLIANT!!! It took some time for technology — and science — to catch up with such revolutionary thinkers, and synthetic biology finally began to take off in 2000.

Really, the idea of synthetic biology (horribly over-simplified) is based on the recognition that biological organisms — no matter how simple — process their environment remarkably quickly, with a resolution and speed beyond anything we, as engineers, have been capable of achieving so far. Another way to think about this is that in this modern age of BIG DATA, for which our greatest challenges are how to store, manage, and analyze the continuous onslaught of exabytes (hunh??) of data, biological organisms had this figured out… well… millions of years ago. Youtube’s streaming video? Got it! Bose’s Quiet Comfort noise canceling earphones? Remember how we all ignored nagging parents or droning lecturers… oh yes, got that. iPhone’s accelerometers? Yup. And what’s even more inspirational or frustrating (depending on which side of the technological line you fall) is that we don’t only do it faster, we do it better.

Then UT Austin Ph.D. student Jeff Tabor (now a prof at Rice University), holding a bacteria-produced photo of an enlarged E. coli bacterium…
Photo by: Marsha Miller, UT Austin

Here’s an example. In 2004, in response to a synthetic biology competition call by the International Genetically Engineered Machine (iGEM) Foundation, a group of students at UT Austin invented a method for making photos out of… bacteria! The basic idea is that they genetically-engineered E. coli bacteria to respond to light, giving them a new biological circuit that would cause them to turn black when growing in dark areas and to turn clear in the light. A reasonable analogy would be to think of each bacterium as a pixel on your computer or TV screen. By then spreading and growing them evenly on a Petri dish as a homogeneous lawn of bacteria, and then projecting lighted images on them, the students could reproduce images using these genetically-engineered bacteria.

Why is this exciting? Well, for all of you owners of the latest iPad, iPhones, and MacBook Pros, your stunningly gorgeous Retina displays have approximately 326 PPI (that stands for “pixels per inch”). In contrast, with the bacterial images developed in 2004 (yes, nine years ago!), we’re talking gigapixels per square inch resolution, or thousands of pixels per inch, to make it more comparable to the PPI unit. That’s an order of magnitude greater than the Retina displays… I mean… WOW!

But, ok. So for all of you super-skeptics out there, why should we care? This is a monochromatic display that can (literally) die, when we’re into vibrant, saturated, archival colors seamlessly (sort of) integrated into our electronics… not to mention that these students had to build a seven-foot tall projector to create these relatively simple-looking images… which don’t even move! (Yes, we can all hear the collective gasp by the MTV generation and onwards.) [A side note to all you curmudgeons:  I still think this is wonderfully cool.]

Analog synthetic and systems biology.
From: R. Sarpeshkar, MIT

Let’s get back to the inspiration for this post. Last week, the journal Nature published an article by Daniel and colleagues from MIT, titled: “Synthetic analog computation in living cells”. While our obsession with the digital processing universe makes this sound like a step back into the Dark Ages, an advantage of analog devices is that they can be simpler while maintaining greater bandwidth and frequency range (yes, think about this from the standpoint of music!). When a signal is converted from analog to digital, it can lose some of its range (or fidelity) depending on the sensors involved, and this conversion process takes time.

Some of you may have heard of the analogy of a biological cell being somewhat like a digital computer, which processes everything as a series of ones and zeros. In reality, however, this is actually a gross oversimplification. While cells do respond to certain stimulants with a binary (on/off) response, the reality is that they use a mix of these digital-like responses and graded responses (think grays, and sorry, I’m not referring to Fifty Shades of Gray) when responding to various inputs — something the digital world of ones and zeros, black and white, cannot do. However, those who have tried to take the cell-computer analogy all the way have been able to use DNA as components for producing digital calculators, sensors and the like. The drawback is that these circuits require an enormous number of components to perform the simplest computations. Each component could be a DNA strand or a protein, which makes the process slower and more difficult to reproduce.

The system that Daniel and colleagues have assembled takes bacterial cells and transforms them into living calculators that can compute logarithms, multiplication, division, and can perform even more sophisticated functions such as acting as an in vivo pH meter… with three or fewer genetic parts. Furthermore, because their system operates in the analog signal processing domain, it can process graded information, characteristic of the natural environment in which we live and with which we interact. Such analog computation could permit the design of cellular sensors for pathogens or toxins. It may now also be possible to combine their analog technology with the digital systems to construct a synthetic digital/analog hybrid system that can swap between the two signal processing approaches according to which mechanism can produce faster or more accurate calculations or processes. Also, from the broader biological context, it now may also be possible to observe the behavior of such a synthetic, analog system and begin to gain a better understanding for how biological systems receive and process complex information, permitting the rapid responses and fine control necessary to make life a brilliant, rapid, high-resolution reality.

What is Innovation?

OK, so I just stole the title of this post from NSF”s first episode of a series they produced in collaboration with the U.S. Patent and Trademark Office and NBC Learn, to explore innovations… and their innovators, around the US. In a fantastic collection of eleven videos, they cover everything from prosthetic exoskeletons (bionic limbs) and 3-D printing,  through smart materials, security, and automation. Ready to learn how these innovators came up with their inventions? Are you ready to be inspired? If so, check out the videos here.

Is Samsung about to become the new… Apple?

Apple’s iPhone vs Samsung’s Galaxy S…
(photo from http://www.businessinsider.com)

Oh boy, oh boy… game on. It’s no news that Apple and Samsung are going head to head in the smartphone and tablet computer industry. Since 2011, they have been involved in at least 50 lawsuits all over the world, with Apple winning some, and Samsung winning others. So, why, exactly, am I now blogging about this, when this is so… like… 2011? Better yet, why is this rivalry suddenly of such interest as to warrant a full story in the Technology section of the New York Times just this last Sunday? Apparently, Samsung actually now has a chance to be a real competitor, no, perhaps even to dominate Apple in the not-too-distant future.

This is a particularly interesting prediction, seeing that Apple still clearly has the market cornered, raking in 72% of the profits in the mobile phone industry and Samsung taking the remaining drippings (Apple and Samsung surprisingly are currently the only two companies turning profits selling mobile phones!). What makes Samsung a potentially lethal competitor is their approach on design.

In 1989, Steve Jobs was named as Entrepreneur of the Decade by Inc. Magazine. Characterized as brash, boyish, and a perfectionist, in his interview with Inc. editors George Gendron and Bo Burlingham, Jobs proclaims that he designs not for what consumers want (they don’t know what they want), but what they might think is impossible. In other words, if you ask consumers what new functionality they want in a gadget, by the time you can deliver that functionality, they are ready for the next step and won’t be satisfied. As a result, in Jobs’ mind, the key to innovative design was to tell consumers what they want before they know it. Clearly, this worked quite well for Apple.

In contrast, Samsung takes a more… traditional approach, using market research to guide trends and innovation. According to Kim Hyun-suk, the executive vice president of Samsung, the company’s modus operandi is to use the market as the driver for product design, and not to drive the market in a certain direction — interesting, considering their extraordinary success with the Galaxy product line, and its reviews claiming its innovative features. Another example: while Apple just recently released the iPhone 5 with a larger screen, Samsung was already selling the 5.3″ screen Galaxy Note. This difference in design philosophy is reflected, also, in the budget allocations at the two companies, with Samsung outspending Apple in R&D, at a nearly 3:1 level ($10.5 billion to $3.4 billion).

What I found particularly notable is Samsung’s approach for design inspiration. They employ 60,000 staff members distributed across 34 research centers in multiple different countries, all saddled with the ultimate task of studying trends in each country and gaining inspiration for ideas. They look far outside electronics for inspiration, including fashion, automobiles, and interior design; and employ designers from a multitude of different backgrounds, including psychology, sociology, economy management, and engineering. Ah, curious… Much as biodesign and the application of biomimetics to idea generation benefits from multidisciplinary diversity, here we have again the melting pot of creative people coming from very different backgrounds, bringing to their design a perspective unique to their training and their lives, creating products with broad appeal and forward-thinking functionality… when the goal is not to drive the market… just a little food for thought.

An eternal conundrum for teachers: How to teach students more… by teaching less?

Image from core77.com

Most students in my Biomimetics/Bioinspiration course are already probably getting tired of hearing me say, “Integration is of the future!! We must learn to communicate across disciplines so that we can collaborate across disciplines. How else do we expect to be innovative if we stay in our own, isolated bubbles?!!?!!?” Considering we are only in our third week of class, this is all a little scary.

I am finally feeling a little vindicated, as someone else out there just might be thinking a little like me. Or, at the very least, he is seeing a broken educational system and is trying to address its problems. Paul Backett,  Ziba’s Industrial Design Director, started a six-part series on one of my fave websites, Core77, discussing design education and how it should and can be revamped or renovated to reflect the tools and challenges of modern technology. He is seeing design students being taught concepts rather than skillsets, and using (consciously or not) technology to be lazy in their craft. Sounding familiar, fellow scientists?

Paul’s MO appears to be to teach design students through full-immersion activities so that they learn through experience rather than by reading textbooks and practicing visualization skills through copy catting an object (see Part 1). In the sciences, there are a few examples of this (e.g., see the CiBER program at UC Berkeley and Stanford’s Design Program, just for starters), but not nearly enough, considering the urgency of the situation.

In the meantime, I am looking forward to following Paul’s posts and gleaning some more wisdom from his thoughts…

STEM-STEAM is it time? Are we ready?

STEM to STEAM Conference, hosted by the Rhode Island School of Design, 20-21 January 2011

I have just returned from a truly stimulating conference co-sponsored by RISD (Rhode Island School of Design) and NSF (National Science Foundation). The conference was entitled, “Bridging STEM to STEAM: Developing New Frameworks for Art/Science Pedagogy.” Attendees included everyone from artists and designers as far-flung as Japan, policy-makers and program officers from NSF, National Endowment of the Arts, and AAAS, accomplished academicians/designers from Brown, RISD, MIT… and then there was me… mesmerized, overwhelmed, and thrilled.

I realize this is not truly a direct discussion of biomimetics or bioinspiration, for that matter, but it is directly related. STEAM is simply a reimagining of STEM (Science, Technology, Engineering, and Mathematics) with Art added in, to signify a new initiative to push for direct collaboration and synergy of the STEM fields with the arts. It also creates a clever, catchy, new acronym. My concern is with the question of whether we, as professionals, academics, students, ready for this collaboration, or are we looking instead at the generation of exactly what the new name suggests: hot air? And if we are ready, what can we do to maximize the success of this wonderful collaboration?

My personal hope is that the combination of art with the sciences will inspire and catalyze progress in both fields. To me, the contribution that art/design can make to the sciences is limitless (and thus a motivation for this blog). In the most obvious connection, art can help with maximizing the visualization and communication of our science. In fact, ask Edward Tufte, and he will probably tell you that the best scientists also have an impeccable design flair combining aesthetics with efficient information communication. See, also, the Nature Methods Points of View column by the Broad Institute’s Bang Wong, for monthly commentary demonstrating how basic design principles facilitate data accessibility. I think all us scientists have a lot to learn from our artist counterparts.

Open source software such as Circos can be used to visualize genomic data in a visually pleasing way while simultaneously enhancing communication. Shown here are ChIP-Seq, chr 22 methylation, whole-genome methylation, multi-species comparison, human genome variation and self-similarity and MLL recombinome. (from Circos website)

A more challenging aspect justifying combining arts with the sciences is in identifying how art can actually accelerate scientific progress. An excellent example of this is the use of animation software such as Maya for pushing forward X-ray Reconstruction of Moving Morphology (XROMM) development, an increasingly valuable tool for biomechanical analyses. Art can also inspire new science, as shown in the PBS documentary “Between the Folds“, in which the ancient art of origami is inspiring mathematics, engineering, and product design.

I leave the challenge of identifying how science can help the arts, to the artists, who can speak more directly about why they would want us in their world… and not for the lack of having ideas about how we can help (think prosthetics and ergonomics, for starters!).

The challenge of the STEM to STEAM conference was to discuss how we can increase the collaborations, to identify the similarities and differences among artists and scientists, and to devise strategies on how to go about bridging the gap… priming the machine, so to speak, for a rather revolutionary change in the way we all think about and do our work.

If you are out there reading this, please weigh in. I would love to hear your thoughts about this matter.

And I now leave you with a video of a project co-produced by one of the conference attendees, Jonathan Harris, called, “I Want You To Want Me.” He is only 30 years old, and already very clearly quite a force to contend with.

The great stone house of Portugal

Photo by Feliciano Guimarães

On the hillside of the Fafe Mountains in Portugal stands A Casa do Penedo, or “the House of Stone”. This amazing home is constructed among four large boulders with walls made of a concrete mix, created to melt the actual house into the flanking boulders. The windows overlook the mountains of Marão.

Although the home is built to blend into its natural surroundings, it still has the basic characteristics of a traditional home, with windows, doors, and a shingled roof, as well as creature comforts such as a fireplace and swimming pool, carved out of the side of a boulder.

Photo by Feliciano Guimarães

Apparently, the home was built in 1974 as a family retreat. However, with the overwhelming interest it has attracted due to its unusual design, the current owner, Vitor Rodrigues, has had to move to seek greater privacy. Also, as a result of problems with frequent break-ins, the home is now reinforced with bullet-proof windows, steel doors, and window grates. However, it apparently still contains a rather cozy interior, as shown by this video.

Janine Benyus at TED conference

OK, so I know that some of you are a bit irked by Janine Benyus because her idealism is sometimes a bit too much (e.g., contrary to Benyus, nature really does generate waste, it is not in reality completely waste-free!). However, this TED talk still has a beautiful message that I wanted to share with you all.

Geeky dreams of an obsessed biomechanist

There are countless stories (legends?) about dedicated faculty who conjure brilliant theories while showering, solve a major molecular roadblock while folding laundry, or dream up innovative interpretations of  complex data. Every time I hear a story like this, I have felt… so envious. But then I  would brush it off with the thought of, “Well, at least I’m not that big of a geek!”

My research strives to understand how we navigate through our complex universe with seemingly barely a thought. After all, how many of us have stood at the edge of a sidewalk in deep contemplation about how much we must flex our ankle, simultaneously activate our gastrocnemius and tibialis anterior, and then absorb the shock with the thick pad of flesh (and fat) on our heels combined with perfectly choreographed knee flexion, as we step down to the asphalt below? Should we have to go through such deep lines of thought, we would undoubtedly all go the way of the indecisive squirrel that gets 3/4 of the way across the road, just to turn around and throw itself under a tire in an effort to return to safety, rather than continue forth to the opposite side of the road a mere couple leaps away. To return to the point, we regularly move across a myriad of different surface types and barely notice it. To top it off, not only do we do it, there are tons of other organisms out there who do it better than we do. What’s going on?

To quantify movement across surfaces, my workhorse is something called kinematic analysis. This basically boils down to marking up an animal with a bunch of points (traditionally drawn on with correction fluid and a fine-tip Sharpie marker), filming with a high speed video, and then going through the record frame-by-frame clicking on each individual point across sometimes as many as 600 frames with 10-15 points per frame. Since our motion analysis is done in 3D, this means we then continue on to repeat this on a second camera (and in some instances, a third). Needless to say, this is a very time-consuming way to collect data, even when it is slightly automated with custom-written tracking software (e.g., see Ty Hedrick’s DLTdataviewer MATLAB program).

We recently purchased a super-duper auto-tracking high speed system to film our animal of choice: lizards. The system consists of six cameras that we mount in a ring, which automatically track reflective markers as the lizard runs through a calibrated filming volume. The amazing part of this system is that it literally can track up to 400+ points so accurately and quickly that we have all our tracked data the second the animal is done running through the field of view. The drawback is that we require markers covered in reflective 3M tape, which gets expensive fast, at $0.40 per mostly non-reusable marker. We are currently marking our animals up with 35-40 points, so burn through points at a rather high rate.

A water dragon with nearly $17 worth of markers, most of which will get soaked off and destroyed in its water dish later that day.

At least one reason for the high cost of these points is that they are literally individually hand-wrapped. Yet, for us “non-professionals” in the way of sticker-wrapping beads, this can be a risky endeavor as the point is useless if it does not effectively reflect light. Additionally, wrapping beads can be extremely time intensive and mentally dull for anyone — including one of our undergraduate helpers — to do. As a result,  I have been in the midst of mental conniptions as of late, trying to figure out an inexpensive, easy way to build markers… all the while watching the dollars fall away as the lizards soak in their water bowls after a hard day’s exercise, destroying the markers so that they are unusable in future studies.

A side view of a tracked model of the lizard shown above running bipedally.

I woke up early this morning — too early by anyone’s standards at 4.30AM — and my brain started whirring. Perhaps it was due to the various discussions we have had in this course, or possibly it was due to one of our recent chapters from Janine Benyus’s book on Biomimetics, but I started seeing bubbles in my half-dream, half-awake state, and gradually began to realize (to my growing horror) that I had become a bona fide geek. These “bubbles” were actually phospholipid balls that were oriented with hydrophobic tails facing inwards and hydrophillic heads facing outwards. It was as if I had returned to Intro Bio my freshman year, only this time, it had really gotten in my head.

When exposed to water, phospholipids will orient the hydrophobic fatty acyl side chains (tails) inwards, away from water, and their hydrophilic heads outwards, forming globules, or balls. Image by Mariana Ruiz Villarreal

As I was lying there confused, disturbed, and exhausted but still determined to stay asleep enough to continue this thought process while awake enough to remember it, I realized that if there were some way to attach reflective glass beads to the hydrophobic heads, I could drop this solution into water to form balls that I could use as quick and easy, highly-reflective markers. Of course, I would also need to find a way to make them solidify so they maintain their shape in air… but that’s just my cynical, awake inner voice talking.

A tent like a leaf

Sketches for a biomimetic tent by Ondrej Vaclavik

I happened to come across these sketches tonight for a biomimetic tent designed by Ondrej Vaclavik, a graduate from Prague’s Academy of Arts, Architecture, and Design.

A top view rendering of the biomimetic tent. Note the clear leaf-like veins!

The structures for this tent are modeled after a leaf, with the veins forming the primary support structures for the tent. Despite the obvious beauty of this structure, it nonetheless is not immediately clear if this offers any added functionality. For example, is it lighter or stiffer? Does it shed water more effectively or deal with wind storms? Alternatively, is this a tent simply constructed for its beauty and to invoke emotions of oneness with the surrounding environment?

Irrespective of this, the design reminded me of tent caterpillars (and other similar insects) that actually will stick two or more leaves together to form a shelter while they pupate. My best guess is that the leaves provide more camouflage than protection, although I could imagine that there could be additional environmental advantages conferred from being wrapped in live, respiring leaves, possibly for temperature or humidity control.

Tent caterpillar cocoon wrapped in leaves (from web.cortland.edu)

Can this design be taken a step further: Are there certain repeatable patterns to the way the leaves or folded and stuck together that can be predictable based on the structural properties of the leaves? Are there any properties to the cell structure and their patterns relative to the veins that can be adapted for addressing construction challenges or for increasing the efficiency/organization of transport?

Interestingly, Mr. Vaclavik also has designed other rather slick looking products inspired by biological shapes, for example, this “cactus juicer”, shown below.

A juicer shaped like a cactus. The edges of the ellipses extract the juice, which is then funneled into the cup below.

Hairy feet and scuttling cockroaches… oh my!

As an undergraduate at Berkeley, I found myself dumbfounded and awestruck by the awesome adhesive powers of gecko toepads. For months, I poured hour after hour into removing single toe pad hairs (setae), sticking them to a filed down insect pin, and pressing them against a thin filament of silver wire. I had already stuck a dead gecko on a smooth door and seen it dangling by a single toe with a heavy metal stapler tied to its hips, so I knew there was something spectacular about its adhesive powers (Note: no animals were injured or tormented to discover this!). Yet, each time I pressed a seta to the wire, absolutely nothing would happen. It took countless late night hours of pushing setae to wires with (an arguably) stupidly optimistic outlook, until suddenly, the seta began to stick!

Much of this motivation and inspiration for continuing onwards in this quest was in no small part due to a particularly spectacular advisor, Dr. Robert Full. In the hopes of having him also inspire all of you with his big dreams and creativity, I’ve posted one of his TED conference talks below. I hope you enjoy this as much as I do!