Scientists Didn't Expect This Lab-Made Cell To Start Evolving On Its Own

Scientists have long been in search of an effective recipe for an entirely lab-made cell. Such a feat would be an enormous breakthrough for our understanding of life and could theoretically improve the way certain medications are delivered or compensate for cell loss in certain diseases. Now, researchers at the University of Minnesota have developed SpudCells, which are the first cells made from synthetic materials that have been able to complete a cell cycle. While a very impressive feat, there are many shortcomings of this model; most notably, it is not self-sustaining, and researchers were required to induce replication. Nonetheless, such an advancement could have great implications for the future of bioengineering.

The SpudCell looks like a membrane-bound drop of water, but inside these microscopic droplets are nine fragments of DNA, totaling 90,000 base pairs (those little parallel circles you see on a classic DNA model) that contain 36 genes in total, which are pieces of DNA that encode for proteins. While that 90,0000 base pairs may sound very impressive, this is actually incredibly small compared to naturally occurring cells. For instance, the smallest known genome belongs to the bacterium Carsonella ruddii, which consists of 159,662 base pairs that include 182 genes. Escherichia coli has more than 4 million base pairs, and the human genome has roughly 3 billion base pairs. So, what could such a tiny lab cell do with that little genetic information, and how did something that simple manage to replicate?

That small genome encodes for certain molecular tags that are presented on the SpudCell's surface. The molecular tags essentially function as docking points for liposomes, which are artificial vesicles that act as delivery trucks, bringing the SpudCell nutrients, enzymes, and important functional structures such as ribosomes. Unlike natural cells, SpudCells do not generate nutrients from within, requiring these external deliveries to survive. In other words, the SpudCell is not self-sustaining.

As mentioned above, SpudCells are the first artificial cells that have been able to complete a cell cycle. One of SpudCell's genes encodes for FLAG, which is a tag on the cell's surface that, after binding a specific large molecule, causes it to split through mechanical stress. Thus, the cell division relies on the large molecule being added to its surrounding solution. Moreover, the genome does not exhibit an even split, and after five generations, 30% of the resulting SpudCells contained the complete genome. Additionally, SpudCells are unable to produce their own ribosomes, which enable protein production. After 5 to 10 divisions, their ribosomes degrade.

Interestingly, when the researchers introduced a favorable mutation that promotes cell growth, the mutated cells replicated to outcompete the others. While this does not equate to evolution, as the mutation was a product of engineering, it does appear that SpudCells select for helpful genetic alterations over the course of subsequent generations. Therefore, the researchers showed that the SpudCell is capable of replication and selection, though artificially induced.

The lead researcher on this project, Kate Adamala, acknowledges that this division process is inefficient. However, she emphasized that there is an opportunity to build on this mechanism to advance synthetic biology. In an article from Science, Adamala compared the SpudCell to the Wright brothers' first attempt at making an airplane. What the research group has created is not a truly "living" synthetic cell, but it has presented a useful stepping stone for other projects. In the future, Adamala's group aims to reduce the SpudCell's reliance on externally derived nutrients, creating something that is more self-sustaining.

It's useful to note that the SpudCell has not avoided controversy. In fact, the paper exhibiting its discovery has yet to be published in a peer-reviewed journal. Ironically, when the initial paper outlining their findings was submitted to the journal Cell, it was rejected. The peer-review process does take a long time, and sometimes researchers will publish their work on bioRxiv so that others in their field can still access their findings while they await publication. However, Adamala took a different approach that has garnered some criticism.

After rejection from Cell, Adamala sent the paper to members of the media as opposed to first opening the piece up to peer-based feedback. As such, the work has garnered a significant amount of interest in the press, but, unlike most studies, has yet to pass the scrutiny of other anonymous experts. However, Adamala stated that the paper will be submitted to another academic journal soon.