The Body Electric

Editor's Note: The annual TED Conference (Feb. 26-Mar. 4) is an invitation-only affair known as the place where high-tech tycoons, Nobel Laureates, and other smart people gather to share ideas that will inspire. The TED Fellows program was established to give people who wouldn't ordinarily have the opportunity—or the means—to present their remarkable work to an audience that just might include Bill Gates and Al Gore. In a series leading up to TED, will feature interviews conducted via e-mail with a handful of this year's fellows.

Nina Marie Tandon
Tissue-engineering researcher
Columbia University Laboratory for Stem Cells and Tissue Engineering
Cooper Union, adjunct professor of electrical engineering

You don't find many electrical engineers working in medical research. Then again, you don't find many engineers inspired by "thoughts of DNA coding and signal transmission."

Nina Tandon says she has always been fascinated by the connections between electricity and the human body.As an undergraduate engineering student she built a digital Theremin, an electronic musical instrument that is "played" by using the electromagnetic waves in our bodies. On a Fulbright scholarship, she worked with a team of researchers on an electronic nose that could "smell" lung cancer.

These days she is teaching a class at Cooper Union (her alma mater) in bioelectricity, going for an executive MBA at Columbia University, and working with other research scientists at Columbia, exploring how electrical stimulation can grow heart tissue.

Q: How do electrical signals stimulate tissue growth?

A: Electrical signals—currents and voltages produced by cells—are pretty much ubiquitous in coordinating and maintaining everyday life. Sensory organs, for example, convert sights, sounds, and smells into electrical signals that can be interpreted by the nervous system, which transmits and interprets these signals. Electrical signals also initiate contractions of the muscles in the gut, skeleton, and heart, and the list goes on.

It's also been known for quite some time that electrical currents can be detected in developing embryos and in wounds. Because the cells that become the heart begin to pulsate very early on in embryonic development, it can be said that the vast majority of the time that an embryo develops is in the presence of electrical signals. And since our cells are filled with dissolved salts, which are charged particles (called ions) any time a cell is "cut," as in a wound, these charged particles spill out and create current (movement of charge) that can be measured and that subsides as the wound heals. What's less known (and is a very active field of research) is how these signals may play a role in directing cellular differentiation, tissue growth, and of course, by extension, to tissue repair and regeneration.

And that's what you're doing in the lab?

In our laboratory, we develop advanced cell culture systems (we call them bioreactors) that mimic the cellular environments encountered in the body. I have devoted a lot of time to studying cell responses to physiologically relevant electrical signals, especially in the heart, which is the body's largest source of electrical energy, much, much bigger than the brain, since it beats as one huge (billions of cells) coordinated mass.

I modulate the amplitudes and frequencies of electrical stimulation that I apply to the cells I grow, trying to coax them into connecting and forming living, beating, and engineered heart tissue.

Is the bioreactor an incubator for tissue growth?

In a word: yes. Bioreactors are a primary tool for mimicking the native environment of the natural body and providing the appropriate cues that can help orchestrate the conversion of a "collection of cells" into a specific tissue. An "incubator" in a lab like ours refers to a box the size of a mini-refrigerator that provides temperature, humidity, and gas control, but this is only the starting point, from our perspective.

Have you actually grown heart tissue? How long does the process take? Is the tissue then grafted onto the heart?

Yep. I can't tell you how amazing it is to see the cells I've spent time culturing start to beat. They are so cute! When I've grown heart tissues from rat cells, it would take about five days for the cells to start beating, and after eight days we had engineered tissues that were remarkably mature. With human cells, it takes longer (two to three weeks typically). A main motivation for the field of cardiac tissue engineering is to generate a "patch" that can be grafted onto the heart like a Band-Aid after heart attack. But this has only been done to date with animal models (e.g. rat, mouse). Of course, a very interesting (and potentially lucrative) intermediate step is to use engineered tissues as a platform to test drugs.

Will we be able to grow spare parts for the human body one day?

If you talk to surgeons, we're going to need products that are ready "off the shelf." For this to happen, we'll need more infrastructure for banked cells, cell culture, and product storage, but it's certainly not inconceivable.

The field of tissue engineering is still quite young—about 20 years. To date there have been a few tissue engineered products that have made it to the clinic. We see some examples of skin-replacement products (such as Dermagraft and Apilgraf) and cartilage (Carticel), but it will be a while before we see anything resembling the "body shop" of replacement parts that we often hear about being just around the corner.

My hope is that the heart tissues we engineer in the lab may someday provide a new solution to regenerate damaged hearts, alleviate the shortage of donors, and test new drugs. In order to transform these tissues into marketed products, however, a lot of work remains to be done in the lab.

All this sounds a little like Frankenstein, if you don't mind me pointing that out. Did you read the novel or see any of the movies?

I read a ton, but I've actually never seen or read Frankenstein. I can't help but notice that tissue engineering has made it into popular culture—into House and Grey's Anatomy. I'd love to consult on the show, though, since there are a few discrepancies (besides cartilage being engineered in a single episode) between TV and real life.

How did you get into this line of research?

I've always been interested in the biology that's behind our experience of the world. Some of this might stem from the fact that, among my siblings, I am the only one with "perfect sight." X-linked eye problems run in my family: My brother has retinitis pigmentosa (RP), seeing very little at night. Both of my sisters are color deficient, seeing brown and green as the same color. As a child, I was mystified that my siblings could not see what was obvious to me. (My sisters made some interesting eye shadow and lipstick choices.) I began to understand at an early age that even our most basic perceptions of the world can differ greatly from one individual to another.

The parallels I observed between engineered systems and human biology continued to intrigue me. When I was working in telecom, for example, I was also taking anatomy and physiology classes at the local community college, and lots of thoughts about DNA coding and signal transmission would inspire me. I love pointing out to my students that the cable equations we use to analyze transmission along nerves are the same ones developed for the transatlantic cable.

You worked on an electronic nose used to "smell" lung cancer? Did you actually build something that looked like a nose? (We're not talking Woody Allen in Sleepers, are we?)

For a Fulbright project, I reached out to a wonderful team at Tor Vergata University in Rome that was building a system called the LibraNose, and they generously took me in. When compared with sight and hearing, which we can argue are detecting "frequencies" and "amplitudes" of waveforms (light and sound), the sense of smell is very complicated. At the time (this was 2003) the LibraNose was constructed as an array of sensors, each of which responded slightly differently to chemical stimuli. Because they all responded a bit differently, they could create an array of these sensors that would respond in a characteristic "signature," and using artificial intelligence [software], a computer system could be "taught" to differentiate between these signatures.

We know that certain illnesses can create odors on the breath, and since lung cancer is actually in the breathing organs, it made sense to deploy the LibraNose on this application. Dogs have been known to be able to smell lung cancer. but as we know, their sense of smell is exceptional.

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