Created the first viable semi-synthetic organism with six bases.

A standard DNA molecule with four bases A, T, G, C. American scientists added synthetic bases X and Y from triphosphates to them. Graphics: Deco Images II / Alamy / Alamy

The natural genetic alphabet of terrestrial life is limited to two base pairs adenine-thymine (AT) and guanine-cytosine (GC). All the diversity of life on the planet is programmed, copied and reproduced using DNA strands formed from all four nitrogenous bases of nucleotides. These bases are the same for everyone - for oak, penguin, butterfly and man, they are only arranged in a different order. That was until 2014, when scientists from the Scripps Research Institute designed the first living organism with six bases on the basis of the E.coli bacterium. The two main pairs A, T, G and C supplemented with a synthetic pair X and Y, which functions together with the natural ones.

Theoretically, such organisms are able to store and transmit more information through DNA than ordinary organisms. And this opens the door to achieving the fundamental goal of synthetic biology: the creation of new life forms and new synthetic functions in existing organisms.

The development of a synthetic base pair X and Y lasted for more than 15 years and ended in success in 2014, when scientists proved the fundamental compatibility of a synthetic base pair with life. They modified the nucleotide transporter (nucleotide transporter) - a tool that helps the triphosphates of the synthetic base pair to be transported across the cell membrane. Thus, theoretically, a living organism could grow and multiply, preserving and copying DNA from natural and synthetic bases from cell to cell.
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But it was too early to talk about full success, because in fact the semisynthetic bacterium in that experiment could not be called healthy. She was slowly growing: she was sharing twice the slower normal bacteria. In addition, at certain stages of cell growth, synthetic bases were very strongly destroyed. According to scientists, this is due to the release of phosphate in the cells. They destroy the synthetic triphosphates that make up the artificial bases. As a result, the semi-synthetic bacterium could not preserve artificial bases in the long period.

In 2014, principal proof of concept (PoC) was made. For full-fledged programming of semi-synthetic organisms, it is necessary that the synthetic bases can be embedded in any place and in any context of the surrounding bases, and that they are reliably preserved there with the growth and reproduction of cells.

By 2016, the authors of the work made the necessary changes to the nucleotide transporter, and also made small changes to the base of Y. As a result, they solved all the tasks with normal growth and reproduction of semi-synthetic bacteria, retaining the base pairs X and Y in any place in the chain. The form of synthetic bases is better recognized by enzymes that synthesize DNA molecules during DNA replication, which simplifies the process of copying synthetic base pairs during cell division.


The synthetic bases dNaM-d5SICS - dNaM-dTPT3, as well as the optimizations of the conveyor belt, are shown schematically in the illustration. The chemical structure of synthetic bases is shown on the left compared to the chemical structure of the natural bases dC - dG

Scientists creatively used the popular gene-editing technique CRISPR-Cas9. As is known, in living organisms, this immune mechanism is designed to insert fragments into the genome that correspond to the signatures of “pest” viruses in the immune system so that the body instantly reacts to the appearance of these pests (immune response). So, scientists have designed the bacterium in such a way that it perceives a cell with DNA without bases X and Y as a “pest” that is instantly destroyed. That is, this organism has a peculiar innate immunity to the loss of synthetic bases. This greatly simplified the task of preserving X and Y and made the new semi-synthetic life truly sustainable in the long term.

Under laboratory conditions, semisynthetic DNA remained unchanged after 60 divisions of the bacterium. This gave scientists a reason to believe that it can persist indefinitely. “We solved the problem at a fundamental level,” said Brian Lamb, one of the authors of the scientific work, who is now conducting research for a commercial company Vertex Pharmaceuticals.

Thus, the first in the history of science is a stable semi-synthetic life form, theoretically capable of synthesizing fundamentally new proteins. This means that engineers can now manipulate all life processes.

In the new incarnation, the semi-synthetic bacterium E.coli has become much more adapted to real life. In theory, this life form can multiply, mutate, and evolve, like all living organisms.

The possibilities of using semi-synthetic organisms are truly endless. People have the opportunity to design and create biological systems with desired properties and functions that have no analogues in a living environment. This is not traditional genetic editing, where a fragment of another person’s genetic code is added to the genetic code of one organism. This is a true full-fledged programming of specific properties that are not found in nature. A qualitatively new stage in the development of genetic engineering: roughly speaking, from copy-paste to writing code from scratch.

We can cite a lot of examples from science fiction works, when living beings are designed to clearly perform their tasks. For example, the Dominion warrior race Jem'Hadar of the intergalactic military superpower, located in the Star Trek gamma quadrant, was genetically engineered for war: they lack self-preservation instinct, and the service of the Founders is the only goal of life; Receiving ketrosil is a special drug made by the Founders.


Warrior Jem'Hadar with a ketrosil tube

According to bioengineers , the development of synthetic biology will help mankind to solve many pressing practical problems: to obtain biofuel from algae, bacterial electricity, new diagnostic products, synthetic vaccines, bacteriophages and probiotics to fight infections, to increase the productivity and sustainability of cultivated plants and animals.

Scientists explain that experiments with new DNA bases are safe, because synthetic bases X and Y are not found in nature, so they can hardly get out of control.

The scientific work was published on January 23, 2017 in the journal Proceedings of the National Academy of Sciences (doi: 10.1073 / pnas.1616443114).