The Immune Bacterium

by | Jan 28, 2022 | Biology

In 2014, the project was launched to make a bacterial cell immune to viral attacks.
Candidate E.coli is transformed (in 2016 we are at 63% of transformation) into strain rE.coli-57: a strain resistant to virus attacks because it has an unconventional genetic code. The first completely immune cell is being born.
Its resistance is given by the passage from a code to 64 codons to one that contains 57, in this way the synthesis of viral proteins would be interrupted for lack of tRNA with anticodonts corresponding to the request and these proteins would come (after a certain time) degraded to release ribosomes. The viral genetic code would remain intraduct until its degreadation and could not exploit a cell that does not have the necessary tRNA to translate it.

A Brief Summary

Is genetic code redundancy really important?

All living beings (and many others) on the planet use a universal code to be able to live: the genetic code; this language has a four-letter alphabet (A, T, G, C) and words made up of three letters (triplets or codons), each of which corresponds to an amino acid (monomer of a protein). The genetic code is said to be redundant: more codons indicate the same amino acid; so for 64 codons available, there are a total of only 20 amino acids.

This is for an error prevention mechanism called third base wobbling: the last base of a codon has more chance of being wrong during replication or translation, therefore if for an amino acid they encode more codons with different end letters the amount of errors possible for an equal rate of replications is lowered.

Protein synthesis is – theoretically – a very simple process: a synthesis machine (ribosome) reads an mRNA string and, one codon at a time, builds a sequence of amino acids corresponding to the codonic sequence of the mRNA, amino acids are transported by tRNA (highly specific transporters that recognize their codon on the mRNA string). Proteins then play the most disparate roles in the cell: protein synthesis machines, membrane-carrying proteins, cell-to-cell junctions, cell-to-matrix junctions, signals, receptors and much more.

Viruses are obligate parasites that inject their own genetic code into a host to replicate it for them, this process is possible because the viral code is the same as the cellular one. The host, unable to recognize the viral fragments from its own fragments, replicates the viral DNA and builds the viral proteins, until it explodes by the amount produced, releasing the new viruses that will attack other cells.
What if viral DNA spoke a language other than the one of the cellular DNA?

A Great Discovery

Bacteria just like the X-Man

Complete immunity to viral attacks is a special achievement from many points of view:
– Pharmaceutical: immunity to viral particles would cut the cost of producing many drugs that are currently being produced to combat these infections;
– Food: in the food industry there are many areas of use of bacteria (lactic fermentation, alcohol, etc.), if a culture is colonized by a virus, both the bacterial colony and the food are to be discarded to avoid epidemics;
– Biomedical: many drugs are produced using substances of bacterial synthesis, the colonization of colonies by viruses renders unusable the colonies themselves, which must be eliminated;
The immunity acquired would save large amounts of money, which could be shifted to areas such as research.

Ostrov’s work is colossal: genetic editing techniques existed, but at the time there was not the slightest possibility of rewriting the internal genome; formally, it works as correcting a text document on the computer, In addition, she and her group were the first to attempt such a course of action, which of course made it impossible to compare with other similar experiments.

Ostrov was a pioneer in her experiment and methodically strenuous in its development.

WHY IS THIS DISCOVERY PROBLEMATIC?

The limits placed on science by ethics and nature

Since the birth of the first organisms the genetic code has remained almost unchanged, its redundancy helps to prevent the appearance of lethal mutations (if a base undergoes a change this could lead to a non-functioning or even harmful protein), the wobble of the third base lowers the danger of point mutations, ensuring a certain margin of harmless error. Eliminating redundancy could make any new mutation potentially lethal, or it could – less likely – induce the appearance of viruses with non-redundant code.

There are also many ethical doubts about the applications of this human experiment; although Dr. Ostrov has never mentioned such a hypothesis, it is not said that human beings immune to viruses can not be created (the process would in any case be very complicated, since the human being has a genetic code 800 times longer than the one of E.coli).

Ethical Boundaries

What is licit to do?

The application of such a modification to humans would lead to creatures resistant to viral attacks. This sets ethical limits on the actual feasibility of the thing: would it still be a human being? If it were possible would it really be done? Would the technique be safe?

At the moment its only application on human cells would be feasible on the cultures that allow to study the course and the cure of tumors, the synthesis of drugs or their testing.
Contrary to what happened in China some time ago, this type of genetic editing is impossible with the current techniques.

Another concern is: does redundancy exists for specific reasons, in making inoffensive viruses are we exposing ourselves to replication errors?
The fundamental question is whether it is right to create a genetically modified human being to resist viral diseases, whether it is ethical to do so and at what price, whether it can actually still be considered a human being.