Creating Artificial Life: Choosing The Right Container

All of us, at some point in our lives, have pondered the perplexing notion of life: What does it mean to be alive? How did life emerge on mother Earth? Is there life in the rest of the universe? These are simple questions without simple answers.

To exemplify their complexity, scientists are still reaching a consensus in even defining life, let alone trying to understand it. In their recent publication, Kasper Spoelstra, Siddharth Deshpande and Cees Dekker from TU Delft (the Netherlands) reviewed attempts to understand life by creating it in the lab (Spoelstra et al. 2018, Curr. Opinion in Biotechnology). They specifically researched the types of containers one could use to form an artificial cell.

The key to understanding life may be found at the smallest level of matter, that of single molecules, and how these molecules interact with each other. The last couple of centuries have seen major breakthroughs in the field of biology, leading to a much deeper understanding of living systems.

In the 1670s, Antonie van Leeuwenhoek from Delft constructed the first microscope, allowing him to study tiny creatures only a few micrometers in length (one micrometer = one-millionth of a meter). Around the same time, Robert Hooke (1665) discovered “cells,” which, as we now know, form the basic unit of all living beings, including us. A century later, Charles Darwin formulated the scientific theory of evolution in his book, “On the Origin of Species” (1859), yet a key question was left unanswered: how did life emerge in the first place?

It took another half century until Alexander Oparin proposed the idea that life arose from a pre-biotic soup of organic molecules (1924) and that the first lifeforms could simply be liquid-like droplets (called “coacervates”) that could grow and divide into multiple similar droplets (1936).

Yet another major discovery in biology was that of Francis Crick, who in 1958 phrased the central dogma of molecular biology. This central dogma entails the observation that in all living cells, the biological information is encoded in molecules of DNA (deoxyribonucleic acid), then transcribed into molecules of RNA (ribonucleic acid), and eventually translated into proteins – the actual workhorses that carry out almost all biological tasks. The 1950s opened up the world of molecular biology which has generated a wealth of information on the complexities of life at the molecular scale.

By now, we have gathered a tremendous amount of information about individual biomolecules that make up the cells. What we now really want to understand is the “sociology of molecules” — how these molecules come together to give rise to life.

One way to approach the monumental task of creating life from scratch is to take the individual non-living components and try assembling a cell from the bottom-up. Following this approach, scientists have recently started to phrase serious proposals with the goal of creating something from individual, non-living components that can be called alive. It remains to be seen whether one can re-engineer a living cell by assembling all these components in such a way so as to exhibit the same behavior as natural cells. With the enormous progress in science and technology, however, this now has become an imaginable goal.

But how should one start to build a synthetic cell? Although quite difficult to define, NASA currently uses the working definition of a living system reading, “a self-sustaining chemical system capable of Darwinian evolution.” Thus, one first needs a container to distinguish the “self” from the external environment, and then fill that nano-container with potential building blocks such as DNA, RNA, and proteins to make it functional. Interestingly, this container does not necessarily have to be made up of the same material as natural cells are made up of.

Life, as we know it, has evolved over billions of years, with a restricted set of materials. Now that we have many more synthetic materials, why restrict ourselves to using only the building blocks that nature uses? The recent publication by (Spoelstra et al. 2018) enlists the minimal requirements of an ideal container, reviews several modern approaches, and classifies them in six major classes.

While the scaffolds made up of common biomolecules such as liposomes (composed of lipids, the same material that makes up the boundary of living cells) and fatty acid vesicles (composed of oil molecules) are one of the more obvious choices, the authors also consider completely artificial systems such as polymersomes (vesicles made up of artificial polymers), droplets (having an artificial oily environment), and colloidosomes (droplets with nanoparticles creating the boundary). The authors notably also include coacervates, which do not have a well-defined physical boundary, as a potential scaffold and conclude that a “hybrid system” of two or more of the mentioned containers will finally suit for future synthetic cells.

Why should we care about artificial life forms in the first place? For one thing, it teaches us about the fundamentals of life and our own history. However, there are also multiple practical reasons. For example, artificial cells have a high potential in medicine, for example, to deliver drugs in a sophisticated fashion. With future artificial cells that will perhaps be able to autonomously grow, divide, and evolve, the applications will be endless and will be limited only by our own imagination.

These findings are described in the article entitled Tailoring the appearance: what will synthetic cells look like?, recently published in the journal Current Opinion in Biotechnology. This work was conducted by Willem Kasper Spoelstra, Siddharth Deshpande, and Cees Dekker from the Delft University of Technology.