Clinical pathologists may not see new diagnostics based on the technology anytime soon, but synthetic DNA could be immune to virus infections

Can DNA of bacteria be manipulated to create new bacteria that can be used to manufacture useful things? Should scientists be creating life from lifelessness? Researchers at University of Cambridge in the UK think so. They have synthesized the entire DNA of E. coli and produced a synthetic life-form that reproduces and behaves very similarly to its naturally-occurring counterpart.

This clearly is a leap forward in the study of synthetic biology. But will clinical laboratories see new diagnostics from the technology? Clinical pathology professionals, microbiologists, and infectious disease specialists are extremely familiar with E. coli. However, in the realm of pathology, it’s common for such research to result in more precise methods of diagnosing disease.

Nevertheless, the New York Times (NYT) noted several potential uses for this technology:

“Viruses may not be able to invade recoded cells. Many companies today use genetically-engineered microbes to make medicines like insulin or useful chemicals like detergent enzymes. If a viral outbreak hits the fermentation tanks, the results can be catastrophic. A microbe with synthetic DNA might be made immune to such attacks.”

Jason W. Chin, PhD, a professor of chemistry and chemical biology at the University of Cambridge in the UK, led the research team. He told the Cambridge Independent the researchers chose E. coli because, “in addition to the strain that leads to a hideous bout of diarrhea and vomiting, E. coli is very useful as a biological model.

“Experiments on hardy, non-pathogenic strains have helped us advance our understanding of biology, and it is used in therapeutics, including to create insulin to treat diabetes, and to treat hemophilia, gout, cancer, and other diseases,” Chin notes.

“E. coli is a real workhouse in biology,” he continued. “So, this is a practical choice both for studying basic biology and for biotechnology.”

Jason W. Chin, PhD (above) is a professor of chemistry and chemical biology at the University of Cambridge in the UK, a Program Leader at the Medical Research Council Laboratory of Molecular Biology (MRC-LMB), and also Head of the Center for Chemical and Synthetic Biology (CCSB). (Photo copyright: Keith Heppell/Cambridge Independent.)

The Cambridge Study

The researchers published their findings in the international science journal Nature.

In their paper, the researchers describe how they recreated a genome that was approximately four-million segments long, and then replaced the bacteria’s original genome with a “recoded genome”—piece by piece.

“It’s a landmark,” Tom Ellis PhD, Director of the Imperial College Center for Synthetic Biology in London, told the NYT. “No one’s done anything like it in terms of size or in terms of number of changes before.” Ellis was not involved in the study.

Genetic code, for any living being, is filled with redundancies that have baffled researchers. Chin, like many others, wondered why. “Because life universally uses 64 codons, we really didn’t have an answer,” Chin told the NYT.

Every gene is made up of combinations of pairs of the four main nucleobases found in the nucleic acid of DNA and RNA. They are:

A single gene can be composed of thousands of these bases. A set of three bases is called a codon.

The synthetic DNA Chin and his team built reduced the number of codons where they could. A Chemistry World article notes, “Using DNA synthesis, [Chin and his team] have rebuilt the entire 4-million-base pair genome of Escherichia coli in which two of the six codons for serine and one stop codon were replaced with synonyms, giving the genome just 61 codons rather than 64. They introduced this synthetic genome, with about 18,000 instances of altered codons, into E. coli cells to create a new strain that they call Syn61.”

Chin plans to further compress the genetic code in future experiments to learn how streamlined it can be and still support life.

Prior to this study, the longest synthetic DNA recorded was about one million segments, so this was a significantly longer strand. When it came time to place it in the bacteria, they had to do it one segment at a time, until the natural genome had been completely replaced.

Initially, there was doubt that the Syn61 organism (shown above growing on an agar plate) would continue to live with the synthetic genome, but it did. It is shaped differently than E. Coli with natural DNA, and it reproduces more slowly. Whether Chin Labs’ discovery will result in new clinical pathology diagnostics remains to be seen. (Photo copyright: Wesley E. Robertson/Stat.)

Expanding the Genetic Alphabet

In addition to this study marking several important “firsts,” this study also has numerous implications for potential future research. As noted above, eventually scientists may be able to recode microbes making them immune to viruses.

Another interesting idea is that synthetic, recoded DNA may mean that researchers could program cells in such a way that their genes won’t work if they escape. “It creates a genetic firewall,” Finn Stirling, a graduate student at Harvard University in the UK, told the NYT.

“The space that codon compression ‘frees up’ in Syn61 might be used to code for non-natural amino acids, giving these organisms a different biochemical basis to natural ones,” the Chemistry World article notes. In other words, the extra space created by removing redundant codons could be used to create drugs, proteins, and enzymes.

“It’s pretty mind blowing that you can expand the genetic alphabet this way. I think we’re pretty far from realizing how much we can do with it, producing things we have never seen before,” Julius Fredens, PhD, a member of the Cambridge research team, told BBC News.

The primary goal of the Cambridge researchers was to learn how to manipulate the DNA of bacteria for the purpose of using those bacteria to manufacture useful things. That’s a different emphasis than using this technology for therapy or diagnosis. But significant new tools for clinical pathology diagnostics have come from lesser discoveries. So, this is research worth following.

­—Dava Stewart

Related Information:

World’s First Synthetic Organism with Fully Recoded DNA Is Created at MRC LMB in Cambridge

Total Synthesis of Escherichia Coli with a Recoded Genome

Scientists Redesigned an Entire Genome to Create the Most Synthetic Life Form Yet

World’s First Living Organism with Fully Redesigned DNA Created

Scientists Created Bacteria with a Synthetic Genome. Is This Artificial Life?

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Artificial Life Form Given ‘Synthetic DNA’With a ‘Recoded’ Bacteria Genome Made from Scratch, Scientists Give Life a New Dictionary