Life Not As We Know It

Well, let’s see. Laat week much of the U.S. and parts of Europe were under a crippling heat dome. The U.S. celebrated its 250^th birthday. And there’s something called the World Cup going on, for those of you who care about such things. But, I mean, really, the news of the week? SpudCell.

It may not look like much, but SpudCell is close to synthetic life. Credit: Orion Venero, Adamala Lab

OK, maybe you missed that one. If you are not a fan of science, or of synthetic biology in particular, news about it might not have shown up in your feeds, or perhaps you thought it was another ploy by the Potato Association of America to get you to buy even more potatoes. SpudCell is something truly new: “the world’s first synthetic cell with a complete life cycle, built entirely from non-living chemical components.”

Take a minute to take that description in.

“SpudCell performs the behaviors often used to tell the living from the inert — it feeds, grows, replicates its genome, divides and undergoes selection — yet it is far simpler than any natural cell and was assembled, part by part, by hand,” the project researchers wrote in a statement.

It was designed and built by researchers at the University of Minnesota, announced last week along with a preprint of their paper. The team was led by Professor Kate Adamala, and the name is either due to its supposed resemblance to a potato or it’s a play on “Sputnik.”

“This is likely the most exciting project I've ever worked on,” said Professor Adamala. “We’ve replicated in chemistry what only used to be possible in biology: the complete set of behaviors of a cell. It proves that the most fundamental functions of life, like growth and replication, do not need a mysterious magical spark.”

Scientists have been working for decades on stripping away genetic material from living cells to try to find the minimum necessary for life, but Professor Adamala and her team went the other way, gradually building up genetic material until it started behaving in ways we’d expect cells to.

The impressive thing is that the team engineered everything SpudCell does. As The Economist put it: “Everything the resulting cells do, they do because of molecules that Dr Adamala’s team put there. That leaves no room for mysteries.” That’s not true when researchers start with living cells.

Drew Endy, a synthetic biologist at Stanford University, told Carl Zimmer of The New York Times, “It’s a cell that was built, not born. It’s constructed, but it does what cells do.”

SpudCell is very basic. The human genome has about 3 million kilobase pairs (kbp); SpudCell has 90. And, instead of a single chromosome, SpudCell’s genome is split across seven separate DNA plasmids, while allows researchers to program various cell functions independently.

Whether SpudCell qualifies it as “life” is murky. Professor Adamala cautioned: “Life is not binary. That’s why I’m hesitant to call this ‘alive.’ There’s no clear line, as much as we would love it to be.”

For example, SpudCell doesn’t make its own ribosomes, using ones from e coli bacteria instead, which means it can only replicate for 5-10 generations before things degrade. It also needs some help feeding, with nutrient-carrying liposomes having to be added regularly. But, still; not bad for 90 kbp.

Other scientists are pretty impressed. “Kate Adamala’s team designed and built a nonliving synthetic cell that is much closer to being ‘alive’ than anything else produced by the bottom-up synthetic cell field,” said John Glass, who leads synthetic cell research at the J. Craig Venter Institute. ”It is dazzling that she has put these things all together.”  

“This is a stunning scientific achievement,” says Roseanna Zia, a computational cell biologist at the University of Missouri.

Prof Tom Ellis, at Imperial College London, told The Guardian the work was probably the field’s “biggest breakthrough in recent times,” further explaining: “Making a synthetic cell helps us understand the exact minimum requirements for life and how life might have emerged from chemistry. It’s also useful as it provides a fully understood system for testing biological circuits and computer models of cellular life.”

Professor Adamala admits that in some ways SpudCell is “as dumb as it gets,” and likens it to the Wright brothers’ first airplane, noting that researchers who start with real cells are “like an engineer that’s given a full Dreamliner without all the plans.” Dr. Endy also used the Wright brothers analogy, telling Mr. Zimmer: “The Wright flyer flying for 12 seconds doesn’t get you a 737. This is just the beginning.”

Professor Adamala, along with Professor Endy and two other researchers, have founded Biotic, a public-benefit nonprofit research organization to further the research. They hope to create a shared technical infrastructure for synthetic cell engineering, with a mission “to responsibly enable and steward foundational advances in bioengineering.”

To help other scientists use SpudCells in their research, the Biotic site includes detailed protocols for building SpudCells. It notes: “While our motivation for this research is to make biology a general purpose technology, usable freely by all, we are currently operating in the sandbox environment.” 

Early days.

Professor Adamala says:

This work is just the beginning. We are showing it’s possible to engineer the basic functions of the cell. To fully realize the promise of this technology – to make it robust and practical – we need combined international effort. The role of Biotic is to focus engineering efforts and make them compatible with a shared chassis. SpudCell is that chassis, and with Biotic setting the protocols for collaboration, we are eager to start applying this technology to serious challenges.

“This work demands our attention, not for what has been produced but for where it leads,” Dr. David A. Relman, a microbiologist at Stanford University, told K.R. Callaway of NYT, adding: “It is creative, disruptive and provocative in revealing what might be possible in the not-so-distant future.”

“Creative, disruptive, and provocative” -- music to my ears.

The University of Minnesota announcement makes clear the hope for synthetic biology in general, and SpudCell in particular:

Cells built from scratch could perform molecular transformations industrial chemistry cannot. That could first transform molecular medicine, building precise therapeutic molecules including drugs incorporating amino acids evolution never used. We could see materials that are grown, rather than synthesized, and manufacturing approaches that operate at biological temperatures, not industrial ones. Underneath it is a truly engineerable platform, which SpudCell provides for the first time.

OK, maybe the researchers didn’t “create life,” but the Wright brothers crashed many times before they succeeded. I love this idea of building from the bottom, and I’m rooting for SpurCell to grow up.