Genetically modified E. coli © iStockphoto.com/Guntars Grebezs
dependent on synthetic nutrients While genetically modified organisms (GMOs) have imparted many benefits on society - including churning out drug ingredients, helping produce biofuels, teaching scientists about human disease, and improving fishing and agriculture - they also have the potential to upset natural ecosystems if they were to escape.
hysical containment of GMOs is
altered genome to date in terms of genome function.
By targeting the proteins that drive the essential
not foolproof, so attention has since turned to
We have not only a new code, but also a new amino
functions of the bacterial cell, the E. coli would be
biocontainment: building in biological safeguards
acid, and the organism is totally dependent on it.”
unable to flourish even if it did escape.
to prevent the organisms from surviving where
The process built on the existing method of
The group grew a total of 1 trillion E. coli cells,
they’re not meant to. In the case of Professor
turning normally self-sufficient organisms like E.
and after two weeks none had escaped. “That’s
George Church of Harvard Medical School’s Wyss
coli into auxotrophs - creatures which can’t make
10,000 times better than the National Institutes
Institute, the secret was making an organism whose
certain nutrients they need for growth. The team
of Health’s recommendation for escape rate for
life was dependent on something only he and his
also made 49 genetic changes to protect against the
genetically modified organisms,” said Church.
group could supply.
possibility that the E. coli could acquire the ability
Church’s team also made the E. coli resistant to
In 2013, Church and his team created the
to synthesise the nutrient over time. According
two viruses, with more to follow. The modifications
world’s first genomically recoded organism - a
to Church, the chance one of the bacteria could
offer theoretically safer E. coli strains that could be
strain of Escherichia coli with a radically changed
randomly undo all of those changes, without also
used in biotechnology applications with less fear
genome. Writing recently in the journal Nature, the
acquiring a harmful mutation, is incredibly slim.
that they will be contaminated by viruses, or cause
scientists reported that they had further modified
These criteria limited Church and his team
the E. coli to incorporate a synthetic amino acid in
to “a small number of genes”, he said. The group
A separate group, led by a Farren Isaacs of Yale
many places throughout their genomes. Without
used computational tools to design proteins that
University (a long-time collaborator of Church’s),
this amino acid - which cannot be created by the
might cause the desired “irreversible, inescapable
has meanwhile been able to engineer the same strain
organism or found anywhere in the wild - the
dependency”. They took the best candidates,
of E. coli to become dependent on a synthetic amino
bacteria are unable to perform the vital job of
synthesised them and tested them in actual E. coli.
acid using different methods. The success of the
translating their RNA into properly folded proteins.
They ended up with three successful redesigned
two studies suggests scientists may one day develop
“We now have the first example of genome-scale
essential proteins - whose combined capacity was
something that, according to Church, “will be so
engineering rather than gene editing or genome
“more powerful than using them separately”,
biologically contained that we won’t need physical
copying,” said Church. “This is the most radically
Church said - and two dependent E. coli strains.
42 | LAB+LIFE SCIENTIST - April 2015
ecological trouble if they spill.
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