The Quest for Creating a Fully Synthetic Organism: An In-Depth Exploration

The scientific community is constantly pushing the boundaries of what is possible in the realm of synthetic biology. While researchers have made significant strides in synthesizing various components of living organisms, such as DNA and proteins, creating a self-sustaining entirely synthetic life form remains a complex challenge.

Complexity Despite Scientific Advancements

While progress in synthetic biology and related fields is ongoing, the intricate processes involved in the origin of life continue to elude comprehensive laboratory recreation. Researchers have managed to synthesize various components of living organisms, but constructing a fully synthetic organism remains a complex endeavor.

Defining the Fully Synthetic Lifeform

One must first define the ground rules of a "fully synthetic" lifeform. Are materials derived from living organisms allowed, or must the process start only with pure elements, inorganic catalysts, and energy? These questions are crucial to understanding the feasibility of creating a fully synthetic organism.

Notable Achievements in Synthetic Biology

One of the most significant steps in this direction was taken by Craig Venter and his colleagues. They created an entirely resynthesized genome for a simple bacterium called Mycoplasma and "booted" it by introducing it into a destroyed Mycoplasma cell. This process involved extensive use of biological materials such as membranes and ribosomes, which complicates the process of creating a fully synthetic lifeform.

In Vitro Translation and Gene Replication

In vitro translation (IVT) systems allow for the translation of mRNAs into proteins. There are commercially available IVT systems that use only recombinant proteins and defined small molecules, making them completely devoid of any cell components. In vitro transcription in prokaryotes can be remarkably simple, with some RNA polymerases being a single protein. This makes adding transcription straightforward.

Building a Defined Replicating System

A Japanese group has developed a completely defined system with significant DNA repair capabilities that can replicate complete circular DNAs as long as the supply of monomers holds out. This system has been shown capable of replicating circles of over a megabase, larger than the genome used by the Venter group.

Challenges and Funding

Despite these advancements, the biggest challenge lies in creating a minimal cell membrane. The lipid bilayers have important asymmetry, and there is the challenge of getting proteins inserted, as protein insertion mechanisms often rely on proteins already inserted in the membrane. Funding for this type of research is painstakingly difficult to secure, with human diseases and cancers receiving the lion's share of grants, making it close to career suicide for many junior faculty.

Limitations in Synthetic Chemistry

Our ability to build large proteins by pure chemistry is quite limited. Progress in this area has been made, but it is still far from sufficient. The idea of building a simple cell entirely with "mirror image" molecules has been seriously proposed and would be amazing. However, we are a long way from achieving this.

In conclusion, while significant strides have been made in synthetic biology, creating a fully synthetic organism remains a complex and challenging endeavor. The field continues to evolve, and with ongoing research and advancements, it may not be too far in our future.