Genetics Synthetic Biology

Scientists create first stable Semisynthetic Organism

Semisynthetic organism

You might have seen movies like x-men, Jurassic Park and many more in which scientists make humans and other animals with extraordinary power (supernatural) that are utterly different from the normal behavior.

Now, Scientists for the first time engineered the ‘semisynthetic organism,‘ by adding unnatural base pairs – X and Y. The new six letters genetic code (DNA) generate novel proteins with unique properties.

How Life Exist

All life form, every living thing, has been built and controlled according to the information in DNA. The DNA itself is made up of four natural nitrogenous bases named adenine (A), cytosine (C), guanine (G), and thymine (T). These DNA bases aligned themselves in a specific sequence determine the structural framework of proteins. The proteins are the strings of amino acids, folded into complex structures and perform the essential cell functions.

Well, in simple words, compare the four natural bases with 26 English Alphabets. What I mean is, just like the alphabets combined to create words and in turn English Language. The same goes for DNA – made of four genetic code, combined to form genes. The genes allow cells to produce amino acids – the basic building blocks of proteins.

Imagine, if the English alphabets had more letters, OR the DNA had more than four natural bases. The story I told you today would be different, might be even more interesting.

New “Artificial Life”

Back in 2014, Dr. Romesberg and his colleagues, at the Scripps Research Institute expanded the natural genetic code to include an ‘X’ and a ‘Y’ in a strain of E.coli bacteria. The unnatural base pairs can be replicated by a bacterium more or less frequently.

“Life on Earth in all its diversity is encoded by only two pairs of DNA bases, A-T and C-G, and what we’ve made is an organism that stably contains those two plus a third, unnatural pair of bases,” said Dr. Floyd E. Romesberg.


Dr Romesberg semisynthetic organism
Professor Floyd Romesberg (right) and Graduate Student Yorke Zhang led the new study at The Scripps Research Institute, along with Brian Lamb (not pictured). Credit: The Scripps Research Institute/Madeline McCurry-Schmidt

In 2017, Dr. Romesberg and his colleagues took their study further in their recently published paper in Nature. They demonstrate how their semi-synthetic cell (E.coli) can hold and process instructions from ‘X’ and ‘Y’ bases while specific new protein and when it divides.

“This is the first time a cell has translated a protein using something other than G, C, A, or T,” Romesberg told Reuters “It’s the first change to life ever made.”

How Genetic Code is Expended

First, the researchers synthesized hundreds of unique nucleotides chemically in the Lab. The new genetic letters are then checked for their abilities to pair with each other selectively.

“And after about 15 years of work, we found two that paired together really well, at least in a test tube. They have complicated names, but let’s call them X and Y.” Dr. Romesberg added.

The second step involves finding a suitable way to insert these X and Y bases into the target cells. Also, find out the protein expressed by unnatural bases does functions similarly in bacteria as they do in algae and so on.

Artificial Organism
Expanding the genetic alphabet. Credit: Synthorx

Why “Semisynthetic Organism”?

Today, Proteins are used for an increasingly broad range of different applications and the most exciting one is protein drugs.

The drugs based on protein have already revolutionized medicine, for example, insulin is a protein that has completely changed how we treat diabetes.

“But the proteins are tough to make, and the only practical way to get them is to get cells to make them for you. So of course, with natural cells, you can only get them to make proteins with the natural amino acids. So, the properties those proteins can have, the applications they could be developed for must be limited by the nature of those amino acids that the protein’s built from.” Dr. Romesberg.

Limitations of “Semisynthetic Organism”

Back in 2014, When Romesberg and his colleagues were expecting that their engineered E.coli could hold those synthetic base letter in their genetic code. But that E.coli bacterium couldn’t do. However, the base pair was kept indefinitely while divided and drop over time. This is limiting the ways the organism could use the additional information possessed in their DNA.

“Your genome isn’t just stable for a day,” said Romesberg. “Your genome has to be stable for the scale of your lifetime. If the semisynthetic organism is going to be an organism, it has to be able to maintain that information stably.”



Ethical Concern

With experiments like these, concern about such modified organisms is inevitable, as described in most of the science-fiction movies.

Meanwhile, D.R Romesberg assured that this work is only meant for single-cell organisms and can only be used for storing genetic information. Also, these X and Y base pairs would not express themselves as these are the non-coding length of the DNA.

“I’d like to emphasize that we have a FAILSAFE mechanism built into this system. If you take these bacteria out of the lab [it] converts back to its normal state.” D.R Romesberg said.

Future Perspective

The next step is to make the “semi-synthetic” cell use these base pairs (X and Y) and proceed the two domains of life, i.e. transcription and translation “This study lays the foundation for what we want to do going forward,” said Zhang, a member of the team lead by D.R Romesberg.


Explore more: Synthetic Biology: Promises and Perils

More information: A semisynthetic organism engineered for the stable expansion of the genetic alphabet,

Journal reference: Proceedings of the National Academy of Sciences

Provided by: The Scripps Research Institute



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