This week a team of scientists published a study in Nature Biotechnology* explaining how they created an artificial jellyfish dubbed a 'medusoid.' Let's be clear: scientists have not built a fully functional living jellyfish from scratch. Rather, they have constructed a thin, flower-shaped sheet of rat heart cells and silicone that mimics the swimming behavior of a juvenile moon jellyfish when subjected to an electric current. Since a medusoid cannot move without assistance, cannot eat and cannot reproduce, it does not qualify as a true jellyfish or any other animal for that matter. Still, the achievement suggests new ways to mimic nature in the lab and perhaps even cobble together a functional synthetic life form.
"We have not yet built a true animal or an organism, but what we made is in a sense alive," explains Kevin Kit Parker of Harvard University who designed the medusoid along with Janna Nawroth and John Dabiri of the California Institute of Technology and their colleagues. "If you keep putting together groups of modified cells, you could make a completely unique life form."
So let's try a little thought experiment. What would it take to build a true artificial jellyfish, one that mimics the real thing in every way?
Jellyfish have bloomed and bobbed in the planet's oceans for at least 500 million years. Compared with animals that evolved later in Earth's history—like reptiles, birds and mammals—jellyfish are minimalists: they survive just fine with relatively few organs. Like most jellyfish, moon jellies (Aurelia aurita), the species that Parker and his colleagues mimicked in their new study, have no hearts, lungs, gills, circulatory system or skeleton. Instead, seawater suffices, supporting the jelly's gelatinous body and flowing through its mouth to distribute diffused oxygen and digested food through radial canals. The elegance of such unencumbered bodies makes building an artificial moon jelly less daunting than reconstructing a more complex animal—but it won't be easy.
Jellyfish are not the strongest swimmers in the seas—they often drift where the currents take them—but they can steer themselves too. To propel itself through the ocean, a moon jellyfish first pushes against the water by contracting its translucent bell—like an umbrella closing—and subsequently relaxes its muscles until its bell floats upwards to form a flat saucer. Contract, relax, repeat. A medusoid does exactly the same thing, with one crucial difference: Whereas a real jellyfish generates electrical impulses to stimulate its muscle cells, a medusoid is entirely dependent on voltage generated by electrodes in its tank. Moon jellies have eight pacemaker cells scattered around the middle of their bodies (just about every jellyfish body part comes in multiples of four). Pacemaker cells keep the jellies' muscles pulsating rhythmically. We have pacemaker cells in our hearts that do the same thing. So do rats. Janna Nawroth thinks it's possible to weave pacemaker cells from a rat's heart into the heart muscle tissue that makes up a medusoid, which might allow the artificial jellyfish to bob on its own, sans electrodes. The upgrade would rely on a technique known as "co-culturing," in which different types of cells are grown together. It's often difficult enough to get one cell type to live happily in the lab, let alone a mixture of different kinds of cells. Think of them as high-maintenance houseplants that are fussy about their neighbors, withering if they do not like their circumstances. Although scientists have not yet mastered co-culturing, they have made impressive advances, cultivating little gardens of gut tissue and bacteria, for example, as well as epithelial cells and immune system cells.
Even if you get a medusoid to swim on its own, it will soon die unless it has a way to nourish its cells. Artificial jellyfish gotta eat too. As a natural consequence of its swimming behavior, a living moon jellyfish creates tiny vortices beneath its bell—little swirling currents that help its four "oral arms" and stinging tentacles drag nutritious plankton towards its mouth and into its central stomach full of seawater and digestive enzymes. From there, water carries nutrients into enclosed canals that rise up and spread across the jelly's body, like the branches of a tree.
Since a medusoid swims like a real moon jelly, it too creates eddies beneath its bell, but it has no tentacles, no way to break down food and no channels to distribute that food to its different tissues. Right now, Parker's medusoid is a two-layered creature of rat cells and silicone. A living jellyfish has three layers: an outer epidermis, an inner gastric lining and, appropriately, a translucent jelly-like middle layer called mesoglea. An artificial jelly would need all three layers to properly contain a stomach and radial canals. Living channels, canals and vessels are notoriously difficult to recreate in the lab, but clever strategies in tissue engineering—particularly with 3D printing—suggest that replicating a jellyfish's digestive system is not too far-fetched. Tiny hair-like structures called cilia line the canals within a jellyfish's body, constantly sweeping back and forth to move water and nutrients along. Researchers have in fact constructed artificial cilia that work almost as well as the real thing. Filling a stomach with digestive enzymes or synthetic gastric juice would be pretty easy; getting the stomach to continuously secrete such enzymes would require bona fide stomach cells or genetically modified ones. Tentacles are not essential if the vortices suck up enough water and plankton—but what's a jellyfish without its stinging skirt?
[caption id="attachment_218" align="alignleft" width="300" caption="Moon jellies in Denmark. Notice their four gonads visible through their translucent bells (Credit: Malene Thyssen, via Wikimedia Commons)"][/caption]
A lattice of neurons known as a nerve net envelops a moon jelly's body. In addition to coordinating muscle movement, these cells communicate with receptors that detect light, gravity, touch and chemicals dissolved in the water. Jellyfish do not necessarily need all of these senses to survive, but they certainly help. Besides, a defining characteristic of animals—and most living things, for that matter—is the ability to sense and respond to changes in the environment. An aptitude for detecting light and orienting oneself accordingly—moving toward the light to search for food or away from the shadow of a predator—would be a huge advantage for an artificial jellyfish. The rat heart cells that comprise a medusoid's body cannot sense light, but scientists have developed a relatively recent technique to endow cells with exactly this talent: optogenetics.
Algae, bacteria and some jellyfish have light-activated ion pumps and channels—proteins that allow charged particles to cross cell membranes. Using viruses to ferry the genes that code for these proteins into blind cells, scientists can make those cells light-sensitive as well. Optegenetics alone is not adequate to make a free-swimming medusoid respond to light with meaningful behaviors. An artificial jellyfish would still need to process that information in some rudimentary way, which requires communication and coordination between the pacemaker cells, heart muscle cells and sensory neurons. And that's just to provide the artificial jelly with a simple form of vision. Giving it taste and touch would require different sensory neurons that also need to communicate with muscle cells. Despite the absence of a brain and complex central nervous system, a jellyfish's impressive array of senses would be especially challenging to replicate.
The largest obstacle to creating a true artificial jellyfish, however, is sex. The ability to reproduce and pass one's genes to a new generation is perhaps the most fundamental feature of all life on earth. A medusoid is sterile. It has no reproductive organs.
A moon jelly has four such organs, called gonads, which sit below its stomach. When some jellyfish reproduce, the males squeeze sperm through their mouths into the water and females suck it back through their mouths into their ovaries. In other species the females squirt their eggs through their mouths, which hook up with sperm in the open water. Moon jellies keep fertilized eggs on the four oral arms that surround their mouth in a kind of temporary nursery. The resulting larvae swim into the ocean, anchor themselves on the seafloor and grow into coral-like polyps. These polyps begin to bud, forming a column of upside-down juvenile jellyfish that fit into one another like a stack of cereal bowls. Eventually these baby jellies break off one by one and swim away.
Theoretically, one could try to engineer functional gonads onto a medusoid, but that would not accomplish much. Even if you made a male and female medusoid and coaxed them to mate, they would not produce more medusoids. Instead, they would make regular moon jelly babies. After all, their gonads produce sperm and eggs containing the genes for living Aurelia aurita, not for medusoids. A medusoid does not have a functional genome. Successfully quilting a working medusoid genome that codes for a hodgepodge of rat heart cells and light-sensitive neurons is beyond current capabilities. Besides, there are no genes for silicone or artificial cilia. As long as medusoids remain dependent on human engineering and synthetic compounds, they will always be outcasts of sorts, relegated to the fringes of the kingdom of life. That's probably a good thing.
Creating an artificial jellyfish that could somehow make viable copies of itself is an exciting prospect—but it's also absolutely terrifying. A few synthetic jellies in the lab might not seem like a huge threat at first. But what if—through well-meaning experiments gone wrong or genuine iniquity—they wound up in the ocean? What if they outcompeted other animals? Enormous blooms of wild jellyfish are already hoarding food supplies and imbalancing ecosystsems. One can envision the headlines: Scientists Create Adorable Artificial Jellyfish. Artificial Jellyfish Goes For Its First Swim. Wow, Artificial Jellyfish Are Doing Really Well For Themselves! Unstoppable Swarms of Synthetic Jellies Overrun the World's Oceans. Human Leaders Surrender To Gallant, Generous, Gooey Overlords. Get Ready for the Season Premiere of So You Think You Can Wobble?...
It's not happening now and it's not happening soon. Remarkable progress in synthetic biology and tissue engineering, however, keeps pushing the possibility of making functional artificial creatures out of the sphere of the improbable and into the open realm of the feasible. Although Parker recognizes that possibility, he makes it clear that true artificial animals—ones that can produce offspring—are not his goal. "That is not my intent," he says. "I have no interest in making something that reproduces. I do hope what we've developed will spur some discussion as to what is responsible and ethical, though."
Nawroth agrees. "It's super ambitious to generate a reproductive animal of this degree of complexity. We should just keep them in puberty, stuck at the flirting stage."
*Scientific American is a part of Nature Publishing Group