Medusa, jellyfish, and tissue engineering

The ‘Medusoid’ is a reverse- tissue-engineered jellyfish designed by a collaborative team of researchers based, respectively, at the California Institute of Technology (Caltech) and Harvard University. From the July 22, 2012 news item on ScienceDaily,

When one observes a colorful jellyfish pulsating through the ocean, Greek mythology probably doesn’t immediately come to mind. But the animal once was known as the medusa, after the snake-haired mythological creature its tentacles resemble. The mythological Medusa’s gaze turned people into stone, and now, thanks to recent advances in bio-inspired engineering, a team led by researchers at the California Institute of Technology (Caltech) and Harvard University have flipped that fable on its head: turning a solid element—silicon—and muscle cells into a freely swimming “jellyfish.”

“A big goal of our study was to advance tissue engineering,” says Janna Nawroth, a doctoral student in biology at Caltech and lead author of the study. “In many ways, it is still a very qualitative art [emphasis mine], with people trying to copy a tissue or organ just based on what they think is important or what they see as the major components—without necessarily understanding if those components are relevant to the desired function or without analyzing first how different materials could be used.” Because a particular function—swimming, say—doesn’t necessarily emerge just from copying every single element of a swimming organism into a design, “our idea,” she says, “was that we would make jellyfish functions—swimming and creating feeding currents—as our target and then build a structure based on that information.”

Oops! I’m not sure why Nawroth uses the word ‘qualitative’ here. It’s certainly inappropriate given my understanding of the word. Here’s my rough definition, if anyone has anything better or can explain why Nawroth used ‘qualitative’  in that context, please do comment. I’m going to start by contrasting qualitative with quantitative, both of which I’m going to hugely oversimplify. Quantitative data offers numbers, e.g. 50,000 people committed suicide last year. Qualitative data helps offer insight into why. Researchers can obtain the quantitative data from police records, vital statistics, surveys, etc. where qualitative data is gathered from ‘story-oriented’ or highly detailed personal interviews. ( I would have used ‘hit or miss,’ ‘guesswork,’ or simply used the word art without qualifying it  in this context.)

The originating July 22, 2012 news release from Caltech goes on to describe why jellyfish were selected and how the collaboration between Harvard and Caltech came about,

Jellyfish are believed to be the oldest multi-organ animals in the world, possibly existing on Earth for the past 500 million years. Because they use a muscle to pump their way through the water, their function—on a very basic level—is similar to that of a human heart, which makes the animal a good biological system to analyze for use in tissue engineering.

“It occurred to me in 2007 that we might have failed to understand the fundamental laws of muscular pumps,” says Kevin Kit Parker, Tarr Family Professor of Bioengineering and Applied Physics at Harvard and a coauthor of the study. “I started looking at marine organisms that pump to survive. Then I saw a jellyfish at the New England Aquarium, and I immediately noted both similarities and differences between how the jellyfish pumps and the human heart. The similarities help reveal what you need to do to design a bio-inspired pump.”

Parker contacted John Dabiri, professor of aeronautics and bioengineering at Caltech—and Nawroth’s advisor—and a partnership was born. Together, the two groups worked for years to understand the key factors that contribute to jellyfish propulsion, including the arrangement of their muscles, how their bodies contract and recoil, and how fluid-dynamic effects help or hinder their movements. Once these functions were well understood, the researchers began to design the artificial jellyfish.

Here’s how they created the ‘Medusoid’ (artificial jellyfish, from the July 22, 2012 Harvard University news release on EurekAlert,

To reverse engineer a medusa jellyfish, the investigators used analysis tools borrowed from the fields of law enforcement biometrics and crystallography to make maps of the alignment of subcellular protein networks within all of the muscle cells within the animal. They then conducted studies to understand the electrophysiological triggering of jellyfish propulsion and the biomechanics of the propulsive stroke itself.

Based on such understanding, it turned out that a sheet of cultured rat heart muscle tissue that would contract when electrically stimulated in a liquid environment was the perfect raw material to create an ersatz jellyfish. The team then incorporated a silicone polymer that fashions the body of the artificial creature into a thin membrane that resembles a small jellyfish, with eight arm-like appendages.

Using the same analysis tools, the investigators were able to quantitatively match the subcellular, cellular, and supracellular architecture of the jellyfish musculature with the rat heart muscle cells.

The artificial construct was placed in container of ocean-like salt water and shocked into swimming with synchronized muscle contractions that mimic those of real jellyfish. (In fact, the muscle cells started to contract a bit on their own even before the electrical current was applied.)

“I was surprised that with relatively few components—a silicone base and cells that we arranged—we were able to reproduce some pretty complex swimming and feeding behaviors that you see in biological jellyfish,” says Dabiri.

Their design strategy, they say, will be broadly applicable to the reverse engineering of muscular organs in humans.

For future research direction I’ve excerpted this from the Caltech news release,

The team’s next goal is to design a completely self-contained system that is able to sense and actuate on its own using internal signals, as human hearts do. Nawroth and Dabiri would also like for the Medusoid to be able to go out and gather food on its own. Then, researchers could think about systems that could live in the human body for years at a time without having to worry about batteries because the system would be able to fend for itself. For example, these systems could be the basis for a pacemaker made with biological elements.

“We’re reimagining how much we can do in terms of synthetic biology,” says Dabiri. “A lot of work these days is done to engineer molecules, but there is much less effort to engineer organisms. I think this is a good glimpse into the future of re-engineering entire organisms for the purposes of advancing biomedical technology. We may also be able to engineer applications where these biological systems give us the opportunity to do things more efficiently, with less energy usage.”

I think this excerpt from the Harvard news release provides some insight into at least some of the motivations behind this work,

In addition to advancing the field of tissue engineering, Parker adds that he took on the challenge of building a creature to challenge the traditional view of synthetic biology which is “focused on genetic manipulations of cells.” Instead of building just a cell, he sought to “build a beast.”

A little competitive, eh?

For anyone who’s interested in reading the research (which is behind a paywall), from the ScienceDaily news item,

Janna C Nawroth, Hyungsuk Lee, Adam W Feinberg, Crystal M Ripplinger, Megan L McCain, Anna Grosberg, John O Dabiri & Kevin Kit Parker. A tissue-engineered jellyfish with biomimetic propulsion. Nature Biotechnology, 22 July 2012 DOI: 10.1038/nbt.2269

Andrew Maynard weighs in on the matter with his July 22, 2012 posting titled, We took a rat apart and rebuilt it as a jellyfish, on the 2020Science blog (Note: I have removed links),

 Sometimes you read a science article and it sends a tingle down your spine. That was my reaction this afternoon reading Ed Yong’s piece on a paper just published in Nature Biotechnology by Janna Nawroth, Kevin Kit Parker and colleagues.

The gist of the work is that Parker’s team have created a hybrid biological machine that “swims” like a jellyfish by growing rat heart muscle cells on a patterned sheet of polydimethylsiloxane.  The researchers are using the technique to explore muscular pumps, but the result opens the door to new technologies built around biological-non biological hybrids.

Ed Yong’s July 22, 2012 article for Nature (as mentioned by Andrew) offers a wider perspective on the work than is immediately evident in either of the news releases (Note: I have removed a footnote),

Bioengineers have made an artificial jellyfish using silicone and muscle cells from a rat’s heart. The synthetic creature, dubbed a medusoid, looks like a flower with eight petals. When placed in an electric field, it pulses and swims exactly like its living counterpart.

“Morphologically, we’ve built a jellyfish. Functionally, we’ve built a jellyfish. Genetically, this thing is a rat,” says Kit Parker, a biophysicist at Harvard University in Cambridge, Massachusetts, who led the work. The project is described today in Nature Biotechnology.

….

“I think that this is terrific,” says Joseph Vacanti, a tissue engineer at Massachusetts General Hospital in Boston. “It is a powerful demonstration of engineering chimaeric systems of living and non-living components.”

Here’s a video from the researchers demonstrating the artificial jellyfish in action,

There’s a lot of material for contemplation but what I’m going to note here is the difference in the messaging. The news releases from the ‘universities’ are very focused on the medical application where the discussion in the science community revolves primarily around the synthetic biology/bioengineering elements. It seems to me that this strategy can lead to future problems with a population that is largely unprepared to deal with the notion of mixing and recombining  genetic material or demonstrations of “of engineering chimaeric systems of living and non-living components.”

1 thought on “Medusa, jellyfish, and tissue engineering

  1. Pingback: Organ chips for DARPA (Defense Advanced Research Projects Agency) « FrogHeart

Leave a Reply

Your email address will not be published. Required fields are marked *