In schools all over the world students learn that the secrets of life are encoded in the DNA molecule. Mainstream science is a true believer in DNA as the only genetic information storage for all the genes of any organism.

It is the ultimate goal for biotechnologists around the world to understand and modify this unique biomolecule. Genetic engineering and its daughter discipline synthetic biology are using tools of molecular biology to construct new DNA molecules, even whole genomes (the sum of all genes in an organism).

When bioengineers produce new DNA in the lab, they can be sure that they may later on introduce this DNA to, for example, bacteria which would then start producing a certain interesting molecule. In other words the DNA can be regarded as a kind of universal language that all organisms “speak” and understand.

The universality has a good and a bad side. Good: bioengineers don’t have to think about the language when constructing new pieces of genetic information (which is already difficult enough), and, they don’t have to fully understand how a cell works and still the DNA is used by the cell. Bad: bioengineers are limited to the “vocabulary” of this language, and, it is difficult to prevent unintended communication between organisms.

For many years scientists have accepted this situation, trying to make the best out of it. But recently, a growing number of researchers and engineers were frustrated about the genetic code provided by nature. They started to explore, if the vocabulary of nature could be augmented. For example, all proteins found in nature consist of chains of different amino acids. The length of the chain may vary, from several dozen to several thousand pieces, but there are always the same 20 types of amino acids used. This means that the genetic information, the ATGCs on the DNA, can only encode 20 different amino acids, a surprisingly small number given that several hundred amino acids have been found in the environment.

Some biologist who study the origin of life on our planet, believe that the very early forms of life billions of years ago, started with only 10 amino acids in their repertoire, adding one after another amino acids during evolution until they arrived today at 20.

A lot of things can be done with the 20 amino acids, but even more could be done if cells had 21, 22 or even more of them at hand. But why bother? One reason to go for an augmented genetic code lies in the new functionality of the novel proteins that could then be generated. In 2010, for example, scientist Nedliko Budisa (now TU Berlin, Germany) and Birgit Wiltschi (now ACIB, Austria) helped students in an Austrian high-school to work on a problem the students had discovered.

 

When brewing beer, starch molecules have to be enzymatically (with proteins) broken down to smaller glucose molecules (which is sugar) before the brewing process can begin. Normally, a natural protein, called amylase, is used to do the job. But in order for this large-scale industrial processes to be efficient (Austrians, like the Danish, drink lot of beer) the starch soup has to be heated up to about 80 degree Celcius in big containers.

Obviously, this uses a lot of energy and produces a lot of green house gases (and this is regardless whether the beer is “organic” or not). Would environmentally friendly people then have to stop drinking beer to save the climate? While some environmentalist might advocate asceticism, the students had a smarter solution, as they want to protect the environment and drink beer. The solution was termed amylase 2.0, which is similar to the natural protein amylase, only that is has 21 amino acids incorporated, one more than the original.

First tests showed, that this new protein was more efficient in breaking down starch to glucose, so when using amylase 2.0 the big starch-soup tanks would not have to be heated to 80 degrees but only 50 or even less, thus saving a significant amount of energy and green house gases.

 

In order to unlock the full potential of augmented 20+ proteins, Nedliko Budisa is now leading a European research project called METACODE, to systematically investigate the scientific basis for augmenting the genetic code. METACODE, consisting of 8 research teams from 5 European countries, also wants to tackle the second problem of working with natural DNA, the unintended communication between organisms. One of the concerns of citizens with respect to genetically engineered organisms and food, is the potential of gene flow from the engineered organism to natural organisms. Gene flow means the naturally occurring exchange of genetic material (mostly) between bacteria. Since bacteria don’t have sex, direct exchange of DNA is a way for them to alter the genetic makeup of their offspring. When genetically engineering bacteria and releasing them into the environment (accidentally or intentionally), however, these new genes will sooner or later find their way to other bacteria.

Some people find the idea creepy that synthetic genes are spread in the environment. In some rare cases, these genes might even be a safety concern. Already in the 1980’s, bioengineers tried to find a way to limit gene-flow and the survival of bacteria outside of safe laboratory settings, but with limited success (which is the main reason that genetically engineered bacteria are not released into the environment until today)

In METACODE researchers look at a second interesting feature of the augmented genetic code, that might help to save this problem. It turns out that two genetic codes that are sufficiently different, are no longer compatible. Genetic information encoded in the natural code, for example, would be meaningless in the genetic code of the augmented kind.

Another linguistic metaphor might help to explain the idea behind it. For several hundred years, the hieroglyphs from ancient Egypts could not be read by anybody. In 1799, during a French war expedition, the now famous Rosetta Stone was discovered, which eventually lead to the deciphering of the hieroglyphs. In a way, the Rosetta Stone provides the

Metacodes to understand different languages, without it we would have never understood hieroglyphs (and theoretically ancient Egyptians would never understand us either).

Now back to biology, the establishment of a second (and third, etc) genetic code could eventually lead to such different biological languages, that bacteria and other organisms running that code, would not be able to understand and communicate each other. This means that, theoretically, any piece of DNA exchanged between them would have no useful information for them. In principle this idea can be extended even beyond amino-acids. Some researchers are now trying to construct new types of DNA, that are slightly different to the original one.

Exchanging the letter D (which stands for the chemical term Desoxyribose) for e.g. and H (which means Hexose a slightly different chemical) turns the DNA into a HNA. This HNA can store genetic information like its old sister, DNA, but any piece of information stored in HNA can not be understood by natural organisms, which all use DNA.

Another attempt is made to exchange the “letters” of the genetic alphabet, the ATGCs (which again stand for particular chemical structures). Recently French and German scientists were able to completely replace for the first time one of the four canonical bases in DNA, Thymine (which is the “T”), with an another base called chloro-uracil. Although these findings are exiting and promising in many ways, researchers are also cautious. They first want to understand these new systems sufficiently before thinking of any real world applications, so that the genetic firewall won’t fire back.