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The biochemical language of life contains synonyms. Just as two words can have the same meaning, different combinations of "letters" in one genome can encode the same substance. Last week, scientists revealed that they had developed a reduced and fully operational version of Escherichia coli by eliminating some of these synonyms (the intestinal bacterium is often used as a model organism in basic research). The work was done by the British Laboratory of Molecular Biology of the Council for Medical Research and published in Nature.
Syn61, as this laboratory bacterium is called, is a double step in synthetic biology: the quest for life from scratch. First, it is the largest synthetic working genome ever built, four times the size of the previous record holder.
Second, it was constructed using 61 rather than 64 codons (the letter combinations that make up the protein-generating instructions for organisms, including humans). By eliminating some of the synonyms of nature, scientists have the ability to insert other instructions, allowing organisms to make molecules that are not found in nature. In other words, creating a living organism with a compressed genetic code is an important step on the path that leads to the life forms of the designers.
The four building blocks, or bases, of DNA are commonly called A, T, C and G (adenine, thymine, cytosine and guanine). They come in triplets called codons and there are 64 possible permutations (4x4x4), such as AGC and TCT. Oddly, several codons seem to have the same goal, suggesting that life has intrinsic redundancy. For example, the two codons above, plus four others, add up to six different recipes to make the same amino acid: serine.
In total, the 64 codons make up a total of 20 amino acids that are variously assembled to make the proteins needed for construction and life, and three codons act as stop signs to stop protein manufacture.
The Cambridge researchers wanted to see if they could reduce some of this overlap. They first recoded the E. coli genome on a computer, in the same way that an author would use a "find and replace" function on a text file. They replaced some codons with their apparent equivalents – a task that involved more than 18,000 substitutions. Three codons were successfully removed, which led to the recipe for a 61-codon genome.
The researchers then assembled this simplified genome with the help of commercially available chemicals. To test its viability, the genome from the laboratory was split into several fragments and inserted into naturally occurring E. coli. These synthetic fragments, designed to usurp the corresponding segments of the natural genome, were then recombined to produce E. coli with fully synthetic DNA. The patchwork creation grows more slowly than its wild cousin but is globally comparable.
Jason Chin, who led the effort for two years, described the breakthrough as "unlocking the code." It is a reference to the late Francis Crick, the co-discoverer of DNA, who described the ubiquity of three-letter codons in terrestrial life as a "frozen accident" of evolution. A team from Harvard University is currently trying to create a genome of 57 codons.
If life can be recoded, then in theory it can be reused – to make biofuels, better drugs, or even to create bacteria that pollute. This is the goal of Craig Venter, the American geneticist who has become a central figure in synthetic biology. He is also trying to reduce life to its bare minimum. In 2016, he managed to create a synthetic cell comprising only 473 genes, the smallest genome of any known independent organism. Even this extreme minimalism was accompanied by mystery: we did not know exactly what 149 of these genes were doing.
Rebuilding life – which usually means investing in organisms created in the laboratory with the means to grow, reproduce and evolve – is technically challenging but also raises important ethical issues. legal and social issues. This is particularly true of Genome Project-Write, an independent, nonprofit effort launched in 2016 to synthesize a human genome.
For some, writing a human genome is a natural sequel to reading, a feat accomplished nearly two decades ago. The benefits of such a project, according to its advocates, include the possibility of growing transplantable organs or cultivating cell lines immunized against viruses. But many fear that such technologies may be misused, perhaps to create a new human life.
It was once easy to dismiss such fears – until the work of the dishonored scientist He Jiankui was revealed. His creation of two babies with a modified genome last year showed that scientists sometimes did the unthinkable. Together, the genome edition and synthetic biology offer us the power to amend, or even rewrite, the book of life. We have not yet had meaningful public discussion about how much we want to exercise it.
The author is a scientific commentator
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