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From Frankenstein to Frog Steaks
By Debra Jones
Story location: http://www.wired.com/news/medtech/0,1286,62385,00.html

02:00 AM Feb. 24, 2004 PT

SAN FRANCISCO -- The image of a Jesus lizard, scampering across the surface of a pond on its hind legs, filled the screen in the auditorium.

"Wouldn't it be great to be able to design something like this?" asked Carlo Montemagno, co-director of the UCLA Institute for Cell Mimetic Space Exploration. Like many nanotech researchers, Montemagno is fascinated by the possibilities of mimicking life to create hybrid devices that combine living tissue with inanimate components.

But as researchers continue to explore ways that tiny bits of living tissue can be harnessed to generate nano-engineered products, others are questioning the ways in which they're blurring the line between organic and inorganic. What is life? Do we have the right to re-engineer it? What are the risks?

These were the questions posed at the Animate (in)Animate symposium Saturday, organized by the Exploratorium, a hands-on, interactive science museum in San Francisco.

Montemagno, recent winner of the Feynman Prize in nanotechnology, has developed muscle-powered micro-electro-mechanical systems, or MEMS, robotic devices about the size of a human hair.

"I use living systems as Legos," organizing them in ways nature didn't think of, Montemagno said.

Montemagno has gotten disassociated animal muscle cells to self-organize and grow into muscle tissue affixed to a silicon base structure. He induces the muscles to become stronger along one side of the silicon substrate, allowing them to contract in pincer-like movements. When transferred to glucose, the half-muscle, half-silicon structures begin to move, propelling themselves along like miniature bionic jellyfish.

Because the muscle MEMS use glucose as fuel, they might someday be used as a source of energy. Their tiny size also may allow them to be used as biosensors or tools to build molecular machines.

But it is "far more complex" than originally thought to create these biological machines, Montemagno said. People thought that if they had all the right chemicals in the right proportions and shook them up in a bag, that they would come alive -- but it doesn't work that way.

One challenge is getting organic substances to bind to inorganic ones, said Evelyn Hu, professor at the University of California at Santa Barbara and co-director of the California NanoSystems Institute.

Hu is working with Angela Belcher of the University of Texas at Austin to figure out whether the animate, or organic, can impose a structure on the inanimate, just as proteins direct the activity of cells in the body. Specifically, Hu said, they are asking, "Can a protein love a semiconductor?" Hu and Belcher are acting as matchmakers, in a sense, trying to determine which of millions of different proteins might be attracted to various semiconducting materials.

For the protein, they use a bacteriophage that has been genetically modified to change the peptides, the building blocks of proteins, manufactured on its tail fibers.

Not only did they discover that certain peptides do, in fact, stick to certain semiconducting materials, but they also found that their attraction is monogamous. In other words, a certain peptide adheres only to a certain semiconducting material.

Also, if the peptides are combined with the precursors of the semiconductor -- such as the salts of zinc and sulfur -- the peptides will affect how the zinc sulfide assembles itself. The semiconducting material adopts the structure and regularity of the bacteriophage's protein coat, somewhat as liquid crystals align in response to an electrical charge -- allowing researchers to construct nanorods, for example.

Eventually, this technique may be used to create electronically active fabric or bio-electronic medical sensors. Also, because the process takes place at room temperature, it may reduce the cost and environmental harm of fabricating semiconductors.

Vladimir Mironov, however, is taking the opposite approach. Rather than using organic materials to direct the production of inanimate material, he is using a machine to assemble living tissue.

Mironov, director of the Shared Tissue Engineering Lab at the Medical University of South Carolina, uses a standard HP ink-jet printer with modified cartridges and software to print "ink" of living cells on "paper" of thermosensitive gel. "It's very important, to get funding nowadays, that you call it nanogel," Mironov said, eliciting laughs from the crowd.

By layering the gel and dots of living cells printed in a circular pattern, Mironov was able to create a 3-D corkscrew pattern of living cells sandwiched between layers of gel. The cells fused, creating a living ring or tube of tissue.

His dream is to create vascularized, perfused tissue. Remaining challenges include learning how to keep the tissue alive, and designing a 3-D blueprint for an organ.

Oron Catts, artistic director of SymbioticA, a collaborative art and science lab at the University of Western Australia in Sydney, is more concerned with the impact of biotech than with its specific possibilities.

He wants to "generate evocative objects for cultural debate" about current biotech research. The role of artists is to "make us disturbed," he said.

Catts' art lab has done its best to come through on that mandate, presenting exhibits of "semi-living worry dolls," pigs wings made from living pig tissue, and fish and chips -- fish neurons grown over silicon chips, which control a robotic arm that draws pictures.

In an exhibit last year in Nantes, France, Catts and his cohorts created victimless steaks. "Many think the French habit of eating frogs is disgusting," Catts said, "and many French think the idea of eating engineered food is revolting. So we decided to combine the two."

The artists rescued four frogs from a meat producer, and used a frog cell line to grow frog steaks. They fed and cared for the steaks, as well as the living frogs, for several months. They then dined on "the ultimate nouvelle cuisine."

The frog steak was gelatinous, Catts said, and the substrate had the texture of fabric. When asked about the taste, he said, "The sauce was good."

Catts says the boundary between what is living and nonliving is very gray, and he hopes, by raising questions about how his team's creations should be disposed of (should they be simply discarded, or buried like pets?), they can inspire a "shift in perspective to care for the nonliving that will apply to other more complex organisms."

Several people who attended the symposium expressed concern about the risks associated with these engineered, semi-living organisms. Montemagno emphasized the low risk that any of these organisms could live outside the lab. "It's bigger than winning the lottery to make something that will compete in the real world," he said.

But Erik Winfree, an assistant professor at Caltech working with computational DNA, compared the current state of bioengineering to the early days of the computer revolution. Just as some computer-science students have created viruses that are very hard to eliminate, he wonders if the next generation of high-school students will tinker with bioengineering.

"It's very difficult to predict where things will go," Winfree said. "The first computer was very, very hard to create. And no one predicted PCs.

"We don't have the equivalent for a bioengineering kit -- yet."

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