Interview
Building Synthetic Life in the Lab
Transforming lifeless molecules into something living in the laboratory. That is the ambitious goal of Wageningen researchers working with scientists from six other Dutch universities and organisations. They have received the Summit grant of 40 million euros from the Netherlands Organisation for Scientific Research (NWO) to work on this research over the next ten years.
The project, called EVOLF, builds on earlier initiatives that started in 2017, but the goal – to build an artificial cell – has not yet been achieved. "From previous research, we know roughly which components we need to build a minimal cell, but getting them to work together is a whole new challenge that we will tackle in Wageningen in the coming years," says Nico Claassens, Associate Professor of Microbiology. Along with Professors John van der Oost and Thijs Ettema, he is working from Wageningen on this major research project. We interviewed him about WUR's role in the project.
Creating life from lifeless biomolecules: how do you approach that?
“It starts with identifying the essential building blocks a cell needs to function. From previous research, we have an idea of these basic elements. These are roughly fifteen modules, including the energy provider, the DNA copying apparatus and a protein producer. In theory, when put together in an enclosed environment, these components should together initiate biological processes that make life possible. We have already assembled these components in a vesicle before, but it has so far remained just a lifeless bag of molecules."
We suspect that we need to use evolution to align the biological building blocks
What will you do differently in the follow-up project to succeed?
“In our initial attempts to create life, we cobbled cells together by mixing building blocks from different domains of life. For instance, the component for cell division came from a bacterium, while we took the DNA copying apparatus from a bacteriophage. These two are not used to working together, whereas, in a cell, these processes must be perfectly coordinated. Evolution has optimised these components to work with their natural partners in the cell. John van der Oost and I suspected that evolution plays a crucial role and that we should use it to fine-tune the biological building blocks to each other. That is what we are going to do now in Wageningen, using Thijs Ettema’s expertise in evolution.”
That sounds complicated.
“Indeed. The problem with the artificial cell is that it is not yet alive or dividing. And it is precisely this cell division, and especially the associated duplication of DNA, that drives evolution. Small errors occur during DNA copying, which sometimes turn out to be beneficial. So, we face a classic chicken and egg problem: to make the cell function, we need well-coordinated cell components, but those only form when they evolve together in a living cell.”
How can you then fine-tune such building blocks to each other?
“We will try to circumvent the problem by ‘hijacking’ living bacterial cells. We replace specific cell components of the bacterium with the simple machinery we designed for artificial cell. As the bacterium grows and divides, our integrated component evolves along with it. We have already studied some individual modules. The next step is to combine multiple modules. The longer they have to work together, the better they become attuned to each other, just like a football team.”
Suppose all this works. The boundary between living and non-living is quite vague. When do you consider something to be (synthetic) life?
“Scientists do not fully agree on what life exactly is. There are countless definitions, each with its own nuances and philosophical considerations. As a consortium, we have debated this extensively, but in the end, we decided to just get started instead of endlessly philosophising about what life is. However, the project does include ethicists and philosophers who are precisely focused on this topic.”
When do you consider the project successful?
“If the artificial cell divides three times within a few days, even if we have to cheat a bit by adding extra nutrients. As long as the cell and all its contents divide, our mission is accomplished.”
The idea and the research have matured
It remains an ambitious project. Honestly, how likely is it that you will actually create life in the lab?
“When Cees Dekker, the project leader from TU Delft, came up with this idea fifteen years ago, other researchers thought it was just a bizarre idea. I too was sceptical when I first encountered the project about eight years ago. But the idea and the research have matured. We are collaborating with scientists across the country and using evolutionary knowledge, modern DNA techniques, and artificial intelligence. The naivety is gone, and that makes me cautiously optimistic. But whether we will actually succeed in the next ten years, I cannot say yet.”
Why are you doing this? What are the benefits?
“Despite centuries of biological research, we still do not know how some biological building blocks interact or how life arises from a collection of molecules. We can only truly understand the principles of life if we can create it ourselves. Moreover, by building life, we will undoubtedly make unexpected and fundamental discoveries that we cannot yet imagine. Additionally, this research can lead to practical applications. With a deeper understanding of the biological principles of cells, we can, for instance, make cells more efficient. Think of cells that deliver drugs in the body or improved 'cellular factories' for producing plastic, ethanol, and insulin.”