#233 – James Smith on why he quit everything to work on a biothreat nobody had heard of

By 80000_Hours @ 2026-01-20T10:16 (+18)

By Luisa Rodriguez   |    Watch on Youtube   |   Listen on Spotify   |    Read transcript

Within two weeks of hearing about this issue, I quit the other work I was doing to focus full time on this…. The main reasons for that were the tractability and neglectedness in combination with the scale of this problem.

At the moment the marginal impact of an extra person working on mirror life is huge. If you’re listening in a lot of countries, you could probably become the expert in policy around mirror life in your country within a few weeks or months of working on this.

— James Smith

When James Smith first heard about mirror bacteria, he was sceptical. But within two weeks, he’d dropped everything to work on it full time, considering it the worst biothreat that he’d seen described. What convinced him?

Mirror bacteria would be constructed entirely from molecules that are the mirror images of their naturally occurring counterparts. This seemingly trivial difference creates a fundamental break in the tree of life. For billions of years, the mechanisms underlying immune systems and keeping natural populations of microorganisms in check have evolved to recognise threats by their molecular shape — like a hand fitting into a matching glove.

Mirror bacteria would upend that assumption, creating two enormous problems:

1. Many critical immune pathways would likely fail to activate, creating risks of fatal infection across many species.
2. Mirror bacteria could have substantial resistance to natural predators: for example, they would be essentially immune to the viruses that currently keep bacteria populations in check. That could help them spread and become irreversibly entrenched across diverse ecosystems.

Unlike ordinary pathogens, which are typically species-specific, mirror bacteria’s reversed molecular structure means they could potentially infect humans, livestock, wildlife, and plants simultaneously. The same fundamental problem — reversed molecular structure breaking immune recognition — could affect most immune systems across the tree of life. People, animals, and plants could be infected from any contaminated soil, dust, or species.

The discovery of these risks came as a surprise. The December 2024 Science paper that brought international attention to mirror life was coauthored by 38 leading scientists, including two Nobel Prize winners and several who had previously wanted to create mirror organisms.

James is now the director of the Mirror Biology Dialogues Fund, which supports conversations among scientists and other experts about how these risks might be addressed. Scientists tracking the field think that mirror bacteria might be feasible in 10–30 years, or possibly sooner. But scientists have already created substantial components of the cellular machinery needed for mirror life. We can regulate precursor technologies to mirror life before they become technically feasible — but only if we act before the research crosses critical thresholds. Once certain capabilities exist, we can’t undo that knowledge.

Addressing these risks could actually be very tractable: unlike other technologies where massive potential benefits accompany catastrophic risks, mirror life appears to offer minimal advantages beyond academic interest.

Nonetheless, James notes that fewer than 10 people currently work full-time on mirror life risks and governance. This is an extraordinary opportunity for researchers in biosecurity, synthetic biology, immunology, policy, and many other fields to help solve an entirely preventable catastrophe — James even believes the issue is on par with AI safety as a priority for some people, depending on their skill set.

The Mirror Biology Dialogues Fund is hiring, including for a deputy director and a role in operations. You can also express your interest for future roles and keep an eye on the MBDF jobs page for future openings.

This episode was recorded on November 5-6, 2025.
Video and audio editing: Dominic Armstrong, Milo McGuire, Luke Monsour, and Simon Monsour
Music: CORBIT
Camera operators: Jeremy Chevillotte and Alex Miles
Coordination, transcripts, and web: Katy Moore

The interview in a nutshell

James Smith, director of the Mirror Biology Dialogues Fund and coauthor of the Science paper on mirror life, argues that mirror bacteria could pose catastrophic risks to humans, animals, and plants — an existential threat that’s entirely preventable if we act now.

Mirror bacteria could evade most mechanisms of immunity

All life on Earth is made up primarily of molecules that use only one of two possible asymmetrical forms. For example, the DNA of all life on Earth uniformly twists clockwise. Mirror bacteria would be built of the same building blocks but in mirror-image forms, creating a fundamental break in the tree of life.

Why immune mechanisms might fail:

• Pattern recognition receptors (the immune system’s first line of defence) depend on molecular shape, and likely wouldn’t bind properly to reversed structures.
• The production of antibodies depends on other immune cells first recognising and processing bacteria. If these steps even partly fail, the adaptive immune system likely won’t get properly activated.
• Failures in even one mechanism of the immune system can lead to fatal infections: analogies from human immunodeficiencies suggest this causes severe susceptibility to bacterial infections.

The asymmetry: Mirror bacteria only need to grow to cause harm, and there appear to be enough “symmetrical” nutrients in the body to support growth. But for immune systems to respond effectively, they need to recognise the threat — and the key recognition and response processes would likely fail.

The risks extend beyond humans:

• Vertebrates and many invertebrates have immune systems that share similar principles, also relying on chiral molecule recognition.
• Plants rely more on physical barriers to block bacteria, so mirror bacteria might struggle to establish systemic infections — but could still potentially enter and spread, including through insect vectors.

Mirror bacteria would be completely immune to viruses, a major natural predator

Populations of wild bacteria are kept in check by predators. Viruses that infect bacteria, for example, outnumber them 10:1. James says we can be “very confident” mirror bacteria would be immune: mirror cells can’t read a normal virus’s genetic code, making infection impossible.

This gives mirror bacteria a massive evolutionary advantage. They could potentially:

• Spread through soil, oceans, and air at relatively low concentrations.
• Create reservoirs of infection in the environment that threaten many species at the same time: exposure to contaminated dust, soil, vegetation, and other animals could be lethal.

Mirror bacteria would also likely be resistant to other predators: protists that normally consume bacteria likely wouldn’t recognise or gain nutrition from mirror bacteria. Many of the mechanisms predators use to kill bacteria and pathogens largely rely on molecular shape and would likely fail. Evolution toward consuming them would take time — and by then mirror bacteria might already be environmentally established.

Countermeasures exist but have serious limitations

What might help:

• Antibiotics: Some are achiral and might work — but everyone (including animals and plants) could need continuous prophylactic use, and current manufacturing capacity is nowhere near sufficient.
• Conjugate vaccines: Could potentially trick the body into making antibodies against mirror molecules — but this alone probably doesn’t overcome other immune deficiencies.
• Mirror phages: Could control but not eliminate mirror bacteria populations (predator-prey dynamics prevent complete eradication).
• Physical defences: PPE, biohardening, early warning systems.

Best realistic outcome: “Protect at least relatively small populations of humans and enough food for us to be able to survive as a species.”

We’re closer to creating mirror life than most people realise — but there’s no real benefit to doing so

Synthetic biologists involved in the Technical Report estimate we’re 10–30 years away, but:

• Only $500 million to $1 billion could potentially be sufficient and accelerate this timeline
• Pioneer geneticist George Church thinks it could happen in the next couple of years
• AI acceleration could speed development, though wet lab work remains intensive

Two research fields must advance before we get there:

• Mirror biochemistry: Making mirror components, especially the mirror ribosome (composed of 54 proteins + 3 RNA molecules). Scientists can already make mirror DNA polymerases, RNA polymerases, and 70% of the ribosome by weight.
• Natural-chirality synthetic cells: Booting up life from completely artificial non-living components.

Scientists wanted to make mirror life because it’s a cool technical project and could potentially scale up the production of mirror molecules for therapeutics that resist immune responses and degradation. But these benefits are tiny: we can already make small mirror molecules without mirror life, and applications for large mirror molecules are unclear. Unlike AI or nuclear technology (massive benefits alongside massive risks), mirror life appears to offer minor benefits but potentially catastrophic risks. This makes prevention more tractable: no powerful economic forces are pushing development forward.

Scientists who wanted to make mirror life now advocate against it

The December 2024 Science paper was coauthored by 38 leading scientists, including several who had previously wanted to create mirror organisms.

The backstory: When some synthetic biologists thought one day making mirror life would be appealing, there were no immunologists or ecologists in the room. The catastrophic implications only became clear once the right interdisciplinary expertise came together.

Scientists like Kate Adamala, who was on a 2019 NSF grant to make mirror cells, are now leading voices calling for prevention. And others agree: a recent summit on responsible biotechnology produced a statement signed by about 100 scientists across all continents that said we shouldn’t go there, and UNESCO’s International Bioethics Committee recommended a precautionary global moratorium.

We can actually prevent this — but only ~10 people are working full-time on it

Three things together could stop the creation of mirror bacteria:

1. Scientists hold a strong norm against work to make mirror life, like norms against human cloning.
2. Precursor technologies — the things that would be developed on the way to making mirror life — are sufficiently governed.
3. Governments take this seriously, deploying the kinds of capabilities they use to stop terrorists from accessing nuclear weapons to the question of mirror life.

The field is extremely neglected: Only about 10 people are working full-time on mirror life risks and governance. As James says, “If you’re listening in a lot of countries, you could probably become the expert in policy around mirror life in your country within a few weeks or months.”

Open questions remain:

• Where exactly should we draw regulatory lines? (Mirror ribosome? Full mirror central dogma?)
• What are effective pathways for governance to mitigate the risks? What combination of law, policy, voluntary commitments, and monitoring would be effective?
• What additional research could help clarify the risks — without taking us closer to the goal of mirror bacteria?

The Mirror Biology Dialogues Fund is hiring, including for a deputy director and a role in operations. You can also express your interest for future roles and keep an eye on the MBDF jobs page for future openings.