A Plastic Eukaryote: One Step Closer to Artificial Life

Ethan France | ethan.france@yale.edu July 1, 2014

In 2010, American biologist Craig Venter created the first cell with a synthetic genome. Two years later, researchers in San Diego created the first artificial cell membrane. Now, scientists have created the first synthetic eukaryote, bringing artificial life one step closer to reality.

From Radboud University in the Netherlands, lead researcher Jan van Hest built his eukaryotic cell from water and plastic polymers. His team’s discovery recreates a vital evolutionary innovation, and promises applications in medicine and industry. In the future, synthetic cells may be used as microfactories, producing drugs and other useful compounds.

Jan van Hest of Radboud University, creator of the artificial eukaryote

Jan van Hest of Radboud University, creator of the artificial eukaryote

Van Hest’s achievement has been long in the making. Scientists dreamt for years of creating artificial life, but that dream remained distant until Venter’s 2010 breakthrough. His team at the Craig Venter Institute in California analyzed the genome of Mycoplasma mycoides, a pneumonia-causing bacterium found in cattle. They used this genetic code as a guideline to create their own. Like programmers, they wrote DNA “script” on a computer, later synthesizing it in the lab and inserting it into bacteria.

In one sense, Venter’s bacteria were the first artificial life-forms. Their DNA was completely synthetic, and they operated on lab-written instructions. But Venter’s organisms, using their original organelles and membranes, were not wholly man-made. Nothing aside from DNA had been modified; the cells themselves were naturally-produced. Venter’s experiments were no doubt revolutionary, but much work remained to be done in the quest for artificial life.

In 2012, further progress was made at UC San Diego, where researchers channeled their focus to the cell membrane. As an essential component of life, the cell membrane is critical in the regulation of transport into and out of the cell, and in maintaining homeostasis. This membrane bounds the space in which cellular reactions occur — without it, life could not exist. Using a new chemical reaction, scientists synthesized cell membranes using phospholipids and metal catalysts.

The significance of this breakthrough was enormous. For one, it brought synthetic organisms one step closer to reality. For another, it elucidated the origin of life itself. Scientists still do not completely understand how the first cells formed from inorganic matter. By producing vital cellular structures from extremely simple ingredients, the California team showed one possible explanation.

In the last few years, artificial life has moved forward by leaps and bounds. Now, the Dutch lab has made one of the most significant breakthroughs yet by creating a synthetic eukaryote. All organisms are divided into two classes, prokaryotes and eukaryotes. Prokaryotic organisms include bacteria and archaea; eukaryotes include plants, animals, and fungi. The basic difference is simple: a prokaryote’s genetic material floats loose in the cell, while a eukaryote’s DNA is bounded by the nucleus. The primary advantage of eukaryosis is compartmentalization.  Eukaryotes divide up their functions between specific organelles — some make energy, some store proteins, some dispose of cellular waste. On the other hand, prokaryotes are forced to carry out all chemical reactions in the cytoplasm. This is far less efficient, especially when it comes to regulation. A eukaryote can easily control material flow to and from the nucleus; a prokaryote cannot.

Eukaryosis was a critical step in evolutionary history. Membrane formation may have kicked off life itself, but organelle formation allowed life to become much more complex. Now, scientists have replicated both of these processes artificially — first the San Diego team with a synthetic cell membrane, and now van Hest’s Dutch team with synthetic organelles – increasing our knowledge of biology’s origins.

How did van Hest and his colleagues recreate one of evolution’s greatest inventions? Like Venter’s team before them, they used a pre-existing structure: in this case, a drop of water. They started by building their “organelles.” Using polymers, they synthesized tiny chemical packages to serve as artificial enzymes. These packages were inserted into a droplet of water, which would represent the cytoplasm. Finally, they added the “cell membrane,” or a plastic polymer applied to the droplet’s surface. The final product contained no DNA, nor could it reproduce, but it performed chemical reactions just as a real cell would.

With these successive innovations in biology, synthetic life is no longer a distant vision. Three independent labs have now created its vital components — DNA, membranes, and organelles. The next step, according to van Hest, is synthesizing the three together. He hopes to produce his next cells out of organic lipids, as the California team has already done. Furthermore, he seeks to create cells that produce their own energy. For this purpose, real organisms use organelles called mitochondria — structures yet to be recreated in the lab. Another major step will be the coding of eukaryotic DNA. Once this is complete, scientists will not need to fabricate organelles at all, because synthetic cells with eukaryotic DNA will produce organelles on their own.

One by one, these challenges may be overcome. It is possible that a fully synthetic organism will appear within the next few decades. For evolutionary biologists who seek to reveal life’s origins, this is an important accomplishment. But artificial life has practical applications relevant to the general public as well. Venter hopes to create bio-factories, or programmed cells that pump out medicinal chemicals. With the right instructions, these cells could produce insulin or other drugs, improving the lives of patients with diabetes and other debilitating conditions around the world.

Other applications lie in industry.  Engineered cells could pump out vaccines, degrade toxic chemicals, and make chemical reagents. They could also help solve environmental problems, dissolving the petroleum produced by oil spills and sucking carbon dioxide from the air. Some suggest this could help offset the effects of global warming.

Eventually, custom DNA scripts may run cells of all kinds. They could see use in agriculture, technology, medicine, pharmaceuticals and more, giving scientists a novel way to produce useful compounds. Van Hest’s research is not the last step toward this goal, nor is it the first. Genetic engineering is here to stay, and cellular engineering may be close on its heels.