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Abstract shapes that look like cells to indicate artificial cells in
synthetic biology.
Abstract shapes that look like cells to indicate artificial cells in
synthetic biology.
1. Home
2. Synthetic Biology
Mirror Bacteria Research Poses Significant Risks, Dozens of
Scientists Warn
Synthetic biologists make artificial cells, but one particular kind
isn't worth the risk.
John Glass, PhD
John Glass Headshot
John Glass, PhD
John Glass, PhD is a synthetic biologist at the J. Craig Venter
Institute. The Venter Institute built bacterial cells with chemically
synthesized genomes, which are widely called the world's first
synthetic cells.
View full profile.
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and
Kate Adamala, PhD
Kate Adamala Headshot
Kate Adamala, PhD
Kate Adamala is a synthetic biologist at the University of Minnesota.
She works in the lab on engineering synthetic cells, and at her desk
on biosafety and security of synthetic biology.
View full profile.
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Dec 12, 2024 | 7 min read
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ABOVE: A number of scientists are calling for a ban on research that
could create mirror bacteria, which pose significant risks to
society. (c)iStock, Galina Kamenskaya
As synthetic biologists, we have spent the last few decades in awe of
the breakthroughs in the field. In the last fifteen years, synthetic
biologists have stored books, images, and even videos in DNA,
developed the ability to modify and engineer genes with remarkable
accuracy, and even created an organism with chromosome designed using
a computer and synthesized in the lab.^1-5
These advances have allowed us to develop effective drugs against
diseases like malaria, innovate lightweight, biodegradable, and
high-strength materials such as artificial spider silk, and bolster
our understanding of how life forms.^6-8 In many cases, these
breakthroughs were unforeseen and would not have happened if
scientists could not conduct their research freely.
However, we recently joined a number of other scientists in calling
for a certain line of research to not be pursued: work that could
result in the creation of "mirror bacteria."^9 These are bacteria
made of all components that natural cells possess, but with every
biopolymer being of opposite stereochemistry. We are passionate
defenders of allowing scientists to conduct their research with as
few limits on intellectual curiosity as possible, and calling for a
ban is not something that we do often or lightly. However, every rule
has exceptions, and this is one of them. Unless compelling evidence
emerges showing that mirror bacteria do not pose unacceptable risks,
we believe research to develop mirror life should not continue.
The Allure of Mirror Life
Life is deeply complex and fascinatingly mysterious. What drew us
toward synthetic biology is precisely how much we can learn about
life--and all the important ways we can employ life--by attempting to
rebuild it from scratch. It is for this reason that both of us have
dedicated much of our careers toward the creation of synthetic
cells.
Cells are the basic building blocks of life. The creation of
synthetic cells by using synthesized molecules to reproduce cell
functions, or by assembling natural molecules into synthetic systems,
can be used to do everything from developing bacteria-based
self-healing concrete to creating a minimal cell that allows us to
investigate the first principles of cellular life.^10,11
Minimal cells are especially valuable because normal cells contain
many different components that can react with many other molecules
and cells in complex ways, making them difficult to use for research
or drug development. Because minimal cells were created by
eliminating genes not required for growth in laboratory culture, they
are incapable of surviving outside of our laboratories. The extreme
simplicity of these minimal cells makes them ideal platforms for
research to understand the basics of life and to understand how drugs
might affect basic cell biology.
For these reasons, in 2018, we, along with others, launched the "
Build-a-Cell" community--a network of researchers that aims to develop
synthetic living cells.^12 It was around this time that we also
started working on the development of a "mirror cell."
Many molecules are chiral, which means they exist in a left-handed
and right-handed form. When you put a chiral molecule in front of a
mirror, their mirror image has a different three-dimensional
orientation. Mirror images of a ball or wine glass can look
identical, but the mirror image of a right hand will look like a left
hand. Nature tends to prefer one of these forms. For example, amino
acids--the building blocks of proteins--tend to exist in a
"left-handed" form. Sugars--the building blocks of carbohydrates--tend
to exist in a right-handed form. The term "mirror molecules" refers
to molecules with the opposite chirality from the form most commonly
found in nature. Unnatural mirror molecules such as right-handed
amino acids or left-handed sugars^ have been made in labs.^13,14
Many of the undesirable reactions that mirror cells avoid depend on
sensing and reacting with chiral molecules. Therefore, cells made up
of mirror molecules would simply not interact with most normal
molecules and cells in the first place. Mirror cells could offer a
promising approach for studying life forms with much less
contamination, or for producing mirror drugs that would not be broken
down or removed by cellular processes in the human body. We began
work on mirror cells to achieve these benefits and more, all of us
were looking forward to seeing this area of research succeed in the
coming decades.
With the right components and nutrients, normal cells could soon be
booted to form living life forms, such as bacteria. Similarly, with
the right components and nutrients, mirror cells could be booted to
form mirror bacteria. This technology is further away, and were it to
happen, it would be an incredibly impressive feat of engineering.
While both of us were initially excited about the prospect of
developing mirror life, when we learned that mirror bacteria might
have an incredibly deadly impact if they were ever introduced into
the wild, we changed our minds.
Why Are Mirror Bacteria Dangerous?
It is often the case that artificial or modified organisms struggle
harder for survival compared to their natural counterparts.
Microorganisms developed in laboratory settings are typically grown
in highly specific conditions and with very particular nutrients
whose composition and concentrations do not reflect the complex and
diverse conditions found in nature. As a result, while laboratory
breaches unfortunately do happen--with hundreds of "possible release"
events per year leading to at least one or two detected infection
events per year--most of those involving artificial or modified
organisms do not result in an outbreak, as they are too 'fragile' to
thrive in the adverse environment of the outside world, making them
easy prey to natural predators such as viruses that target bacteria
(bacteriophages).^15
However, many interactions between organisms and cells depend on
being able to sense and react with chiral molecules in the first
place. Their incompatibility with natural biological reactions would
leave mirror bacteria with no natural predators in the wild, as they
could not be sensed, killed, or digested by bacteriophages or other
organisms. Crucially, many of the immune responses in humans, other
animals, and plants also work by sensing and reacting with chiral
bacterial molecules. If a human were to be infected with mirror
bacteria, it could be as if they were immunocompromised, as their
immune systems would face great difficulty in detecting or killing
the mirror cells. As a result, mirror bacteria could hypothetically
replicate to extremely high levels in the human body, causing
conditions similar to septic shock.
The downside of having a biology that renders mirror bacteria
'invisible' to natural enemies is that they would not be able to
consume many of the chiral nutrients found in nature. However,
several nutrients, such as glycerol, are achiral (they do not have
mirrored forms), and thus could be consumed by mirror bacteria.
Well-intentioned scientists could also engineer mirror bacteria that
can consume naturally occurring chiral molecules such as sugars and
amino acids.
In turn, mirror bacteria could spread throughout the environment
without natural predators, infect organisms without triggering much
of their immune response, and possibly cause fatal infections. An
unstoppable replicating mirror bacteria free in the environment could
cause consequences that are disastrous.^16
The Exception, Not the Rule
We are deeply passionate about all synthetic biology has to offer. We
share concerns about the dangers of restricting science because it
goes against political interests, because it is seen as unhelpful, or
because it is simply misunderstood. Free science is usually better
for the world.
However, there are important exceptions. We restrict research
involving live smallpox virus, dangerous human psychological
experiments, and nuclear explosive testing in the environment because
it is too dangerous. We think that the creation of mirror life falls
into the same class of research that is simply too risky to conduct.^
17-19
However, we believe that regulations on mirror biology should not
affect the vast majority of synthetic biology research in medicine or
the pharmaceutical industry. Very few laboratories are interested in
the creation of mirror life, and it is not clear to us that the
development of mirror life offers unique benefits we cannot achieve
any other way. For example, we noted that mirror molecules offer
promise for pharmaceuticals because they can avoid detection by the
body. But many of these mirror proteins, mirror carbohydrates, and
other small mirror molecules are already made in a safe manner, and
with no applications towards the creation of mirror life.^20,21 While
there should be measures in place to ensure large mirror molecules
(such as mirror genomes) are not created to develop mirror life,
research into small mirror molecules should continue freely.
Ultimately, the best way to ensure synthetic biologists continue
developing breakthroughs is to ensure we do not jeopardize global
safety, damage public trust, or cause science to result in tremendous
amounts of harm. Curiosity is not a good enough reason to create
something that could be so dangerous. For the good of mankind--and
science itself--we must avoid the creation of mirror life.
[ ]References
1. Church GM, et al. Next-generation digital information storage in
DNA. Science. 2012;337(6102):1628.
2. Lim CK, et al. A biological camera that captures and stores
images directly into DNA. Nat Commun. 2023;14:3921.
3. Shipman SL, et al. CRISPR-Cas encoding of a digital movie into
the genomes of a population of living bacteria. Nature. 2017;
547:345-349.
4. Jinek M, et al. A programmable dual-RNA-guided DNA endonuclease
in adaptive bacterial immunity. Science. 2012;337:816-821.
5. Hutchison CA, et al. Design and synthesis of a minimal bacterial
genome. Science. 2016;351:aad6253.
6. Zhao L, et al. From plant to yeast-advances in biosynthesis of
artemisinin. Molecules. 2022;27(20):6888.
7. Dou Y, et al. Artificial spider silk from ion-doped and twisted
core-sheath hydrogel fibres. Nat. Commun. 2019;10:5293.
8. Sozen B, et al. Reconstructing aspects of human embryogenesis
with pluripotent stem cells. Nat. Commun. 2021;12:5550.
9. Adamala KP, et al. Confronting risks of mirror life. Science.
2024.
10. Nodehi M, et al. A systematic review of bacteria-based
self-healing concrete: Biomineralization, mechanical, and
durability properties. J. Build. Eng. 2022;49:104038.
11. Heili JM, et al. Controlled exchange of protein and nucleic acid
signals from and between synthetic minimal cells. Cell Systems.
2024;15:49-62.
12. Frischmon C, et al. Build-a-Cell: Engineering a Synthetic Cell
Community. Life. 2021;11.
13. Radkov AD, Moe LA. Bacterial synthesis of D-amino acids. Appl.
Microbiol. Biotechnol. 2014;98:5363-5374.
14. Xia TY, et al. Synthesis of l-glucose and l-galactose derivatives
from d-sugars. Chin. Chem. Lett. 2014;25:1220-1224.
15. Manheim D, Lewis G. High-risk human-caused pathogen exposure
events from 1975-2016. F1000Res. 2021;10:752.
16. Adamala KP, et al. Technical report on mirror bacteria:
Feasibility and risks Stanford Digital Repository. 2024.
17. Research using live variola virus. https://www.who.int/activities
/research-using-live-variola-virus.
18. Research must do no harm: new guidance addresses all studies
relating to people. Nature. 2022;606:434.
19. Limited Test Ban Treaty (LTBT). U.S. Department of State. https:/
/2009-2017.state.gov/t/avc/trty/199116.htm.
20. Zhao L, Lu W. Mirror image proteins. Curr. Opin. Chem. Biol.
2014;22:56-61.
21. University of Texas at Arlington. Mirror-image chemicals may
revolutionize drug delivery. Science Daily. 2024.
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Keywords
---------------------------------------------------------------------
Artificial cell
bacteria
chirality
Meet the Authors
---------------------------------------------------------------------
John Glass Headshot
John Glass, PhD
John Glass, PhD is a synthetic biologist at the J. Craig Venter
Institute. The Venter Institute built bacterial cells with chemically
synthesized genomes, which are widely called the world's first
synthetic cells.
View full profile.
Kate Adamala Headshot
Kate Adamala, PhD
Kate Adamala is a synthetic biologist at the University of Minnesota.
She works in the lab on engineering synthetic cells, and at her desk
on biosafety and security of synthetic biology.
View full profile.
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