Technical Report on Mirror Bacteria: Feasibility and Risks

By Aaron Gertler 🔸 @ 2024-12-12T19:07 (+218)

This is a linkpost to https://purl.stanford.edu/cv716pj4036

Science just released an article, with an accompanying technical report, about a neglected source of biological risk.

From the abstract of the technical report:

This report describes the technical feasibility of creating mirror bacteria and the potentially serious and wide-ranging risks that they could pose to humans, other animals, plants, and the environment... 

In a mirror bacterium, all of the chiral molecules of existing bacteria—proteins, nucleic acids, and metabolites—are replaced by their mirror images. Mirror bacteria could not evolve from existing life, but their creation will become increasingly feasible as science advances. Interactions between organisms often depend on chirality, and so interactions between natural organisms and mirror bacteria would be profoundly different from those between natural organisms. Most importantly, immune defenses and predation typically rely on interactions between chiral molecules that could often fail to detect or kill mirror bacteria due to their reversed chirality. It therefore appears plausible, even likely, that sufficiently robust mirror bacteria could spread through the environment unchecked by natural biological controls and act as dangerous opportunistic pathogens in an unprecedentedly wide range of other multicellular organisms, including humans.

This report draws on expertise from synthetic biology, immunology, ecology, and related fields to provide the first comprehensive assessment of the risks from mirror bacteria. 

Open Philanthropy helped to support this work and is now supporting the Mirror Biology Dialogues Fund (MBDF), along with the Sloan Foundation, the Packard Foundation, the Gordon and Betty Moore Foundation, and Patrick Collison. The Fund will coordinate scientific efforts to evaluate and address risks from mirror bacteria.

It was deeply concerning to learn about this risk, but gratifying to see how seriously the scientific community is taking the issue.

Given the potential infohazards inherent to a project like this, I imagine Forum readers might be interested in the rationale for public release. This question was discussed on page (iv) of the technical report.

The publications contain a lot more information about these risks and analysis from the scientists involved. If you have additional questions, I might be able to source an answer, but I can’t promise I’ll be able to respond and may take a while to do so. Thank you for understanding.

Habryka @ 2024-12-12T19:23 (+48)

Copying over the rationale for publication here, for convenience: 

Rationale for Public Release

Releasing this report inevitably draws attention to a potentially destructive scientific development. We do not believe that drawing attention to threats is always the best approach for mitigating them. However, in this instance we believe that public disclosure and open scientific discussion are necessary to mitigate the risks from mirror bacteria. We have two primary reasons to believe disclosure is necessary:

1. To prevent accidents and well-intentioned development

If no serious concerns are raised, the default course of well-intentioned scientific and technological development would likely result in the eventual creation of mirror bacteria. Creating mirror life has been a long-term aspiration of many academic investigators, and efforts toward this have been supported by multiple scientific funders.1 While creating mirror bacteria is not yet possible or imminent, advances in enabling technologies are expected to make it achievable within the coming decades. It does not appear possible to develop these technologies safely (or deliberately choose to forgo them) without widespread awareness of the risks, as well as deliberate planning to mitigate them. This concern is compounded by the possibility that mirror bacteria could accidentally cause irreversible harm even without intentional misuse. Without awareness of the threat, some of the most dangerous modifications would likely be made for well-intentioned reasons, such as endowing mirror bacteria with the ability to metabolize á´…-glucose to allow growth in standard media.

2. To build guardrails that could reliably prevent misuse

There are currently substantial technical barriers to creating mirror bacteria. Success within a decade would require efforts akin to those of the Human Genome Project or other major scientific endeavors: a substantial number of skilled scientists collaborating for many years, with a large budget and unimpeded access to specialized goods and services. Without these resources, entities reckless enough to disregard the risks or intent upon misuse would have difficulty creating mirror bacteria on their own. Disclosure therefore greatly reduces the probability that well-intentioned funders and scientists would unwittingly aid such an effort while providing very little actionable information to those who may seek to cause harm in the near term.

Crucially, maintaining this high technical barrier in the longer term also appears achievable with a sustained effort. If well-intentioned scientists avoid developing certain critical components, such as methods relevant to assembling a mirror genome or key components of the mirror proteome, these challenges would continue to present significant barriers to malicious or reckless actors. Closely monitoring critical materials and reagents such as mirror nucleic acids would create additional obstacles. These protective measures could likely be implemented without impeding the vast majority of beneficial research, although decisions about regulatory boundaries would require broad discussion amongst the scientific community and other stakeholders, including policymakers and the public. Since ongoing advances will naturally erode technical barriers, disclosure is necessary in order to begin discussions while those barriers remain formidable.

Jackson Wagner @ 2024-12-12T22:59 (+66)

IMO, one helpful side effect (albeit certainly not a main consideration) of making this work public, is that it seems very useful to have at least one worst-case biorisk that can be publicly discussed in a reasonable amount of detail.  Previously, the whole field / cause area of biosecurity could feel cloaked in secrecy, backed up only by experts with arcane biological knowledge.  This situation, although unfortunate, is probably justified by the nature of the risks!  But still, it makes it hard for anyone on the outside to tell how serious the risks are, or understand the problems in detail, or feel sufficiently motivated about the urgency of creating solutions.

By disclosing the risks of mirror bacteria, there is finally a concrete example to discuss, which could be helpful even for people who are actually even more worried about, say, infohazardous-bioengineering-technique-#5, than they are about mirror life.  Just being able to use mirror life as an example seems like it's much healthier than having zero concrete examples and everything shrouded in secrecy.

Some of the cross-cutting things I am thinking about:

  • scientific norms about whether to fund / publish risky research
  • attempts to coordinate (on a national or international level) moratoriums against certain kinds of research
  • the desirability of things like metagenomic sequencing, DNA synthesis screening for harmful sequences, etc
  • research into broad-spectrum countermeasures like UVC light, super-PPE, pipelines for very quick vaccine development, etc
  • just emphasising the basic overall point that global catastrophic biorisk seems quite real and we should take it very seriously
  • and probably lots of other stuff!

So, I think it might be a kind of epistemic boon for all of biosecurity to have this public example, which will help clarify debates / advocacy / etc about the need for various proposed policies or investments.

Denkenberger🔸 @ 2024-12-15T02:15 (+4)

By disclosing the risks of mirror bacteria, there is finally a concrete example to discuss, which could be helpful even for people who are actually even more worried about, say, infohazardous-bioengineering-technique-#5, than they are about mirror life.  Just being able to use mirror life as an example seems like it's much healthier than having zero concrete examples and everything shrouded in secrecy.

 

I think it's true that a lot of topics are not discussed because of concerns about info hazard. But I do think we already had some concrete examples, such as some hotly debated gain of function cases, considering the possibility of something as infectious as measles but as fatal as rabies, or Myxomatosis killing 99% of rabbits.

Eva Lu @ 2024-12-23T07:51 (+1)

I didn't realize people in biosecurity were worried about infohazards. In EA circles I hear biosecurity talked about much less than the other cause areas, and now I'm wondering how much of that is the cloak of secrecy and how much is the field simply being neglected?

Jackson Wagner @ 2024-12-24T00:18 (+8)

Infohazards are indeed a pretty big worry of lots of the EAs working on biosecurity: https://forum.effectivealtruism.org/posts/PTtZWBAKgrrnZj73n/biosecurity-culture-computer-security-culture

JMonty🔸 @ 2024-12-12T20:05 (+31)

There is also this essay from Jason Crawford and this piece from Asimov Press that are less technical description of the Science article

Mo Putera @ 2024-12-13T15:11 (+12)

I appreciated these parts of Jason's article, and am curious if others have a different take:

What to do?

The article recommends that humanity avoid creating mirror bacteria, even as a scientific experiment, no matter how tight the biosecurity around it (which can never be perfect). Funders should not fund such research; governments should even ban it.

This is a simple cost-benefit calculation. On the cost side, the threat is plausible, and the potential damage incalculable. Thus, the risk is immense. On the benefit side, there is no crucial goal for humanity that is known to be enabled by mirror life. Restricting this research would not fundamentally impede progress in biology or bioengineering generally.

Not all forms of mirror biology would even need to be restricted. For instance, there are potential uses for mirror proteins, and those can be safely engineered in the lab. The only dangerous technologies are the creation of full mirror cells, and certain enabling technologies which could easily lead to that (such as the creation of a full mirror genome or key components of a proteome).

In short, by pruning off a relatively small branch of the tech tree, we can avoid a true existential risk.

The article also recommends research to develop surveillance and countermeasures, in case humanity ever does encounter mirror bacteria. This research can be advanced significantly without creating full mirror cells.

We have time to react

Given that the threat is relatively distant, no immediate action is needed. We have time to discuss it thoroughly, among a wider set of participants. The article released today is meant to be the beginning of that wider conversation, not a call to urgent action.

Jeff Kaufman 🔸 @ 2024-12-12T19:23 (+15)

Thanks for sharing this, Aaron!

I agree the "Rationale for Public Release" section is interesting; I've copied it here:

Releasing this report inevitably draws attention to a potentially destructive scientific development. We do not believe that drawing attention to threats is always the best approach for mitigating them. However, in this instance we believe that public disclosure and open scientific discussion are necessary to mitigate the risks from mirror bacteria. We have two primary reasons to believe disclosure is necessary:

  1. To prevent accidents and well-intentioned development If no serious concerns are raised, the default course of well-intentioned scientific and technological development would likely result in the eventual creation of mirror bacteria. Creating mirror life has been a long-term aspiration of many academic investigators, and efforts toward this have been supported by multiple scientific funders.1 While creating mirror bacteria is not yet possible or imminent, advances in enabling technologies are expected to make it achievable within the coming decades. It does not appear possible to develop these technologies safely (or deliberately choose to forgo them) without widespread awareness of the risks, as well as deliberate planning to mitigate them. This concern is compounded by the possibility that mirror bacteria could accidentally cause irreversible harm even without intentional misuse. Without awareness of the threat, some of the most dangerous modifications would likely be made for well-intentioned reasons, such as endowing mirror bacteria with the ability to metabolize á´…-glucose to allow growth in standard media.

  2. To build guardrails that could reliably prevent misuse There are currently substantial technical barriers to creating mirror bacteria. Success within a decade would require efforts akin to those of the Human Genome Project or other major scientific endeavors: a substantial number of skilled scientists collaborating for many years, with a large budget and unimpeded access to specialized goods and services. Without these resources, entities reckless enough to disregard the risks or intent upon misuse would have difficulty creating mirror bacteria on their own. Disclosure therefore greatly reduces the probability that well-intentioned funders and scientists would unwittingly aid such an effort while providing very little actionable information to those who may seek to cause harm in the near term. Crucially, maintaining this high technical barrier in the longer term also appears achievable with a sustained effort. If well-intentioned scientists avoid developing certain critical components, such as methods relevant to assembling a mirror genome or key components of the mirror proteome, these challenges would continue to present significant barriers to malicious or reckless actors. Closely monitoring critical materials and reagents such as mirror nucleic acids would create additional obstacles. These protective measures could likely be implemented without impeding the vast majority of beneficial research, although decisions about regulatory boundaries would require broad discussion amongst the scientific community and other stakeholders, including policymakers and the public. Since ongoing advances will naturally erode technical barriers, disclosure is necessary in order to begin discussions while those barriers remain formidable.

When to work on risks in public vs private is a really tricky question, and it's nice to see this discussion on how this group handled it in this case.

Habryka @ 2024-12-12T19:29 (+1)

I was first! :P

Jeff Kaufman 🔸 @ 2024-12-12T21:15 (+9)

They both show up as 2:23 pm to me: is there a way to get second level precision?

Habryka @ 2024-12-12T21:22 (+6)

You can sort by "oldest" and "newest" in the comment-sort order, and see that mine shows up earlier in the "oldest" order, and later in the "newest" order.

Lorenzo Buonanno🔸 @ 2024-12-12T22:14 (+10)

You can also right-click → inspect element on the time indicator:
 

Tyler Whitmer @ 2024-12-19T15:56 (+3)

This has to be the best "FIRST" debate ever.

JP Addison🔸 @ 2024-12-12T21:33 (+6)

I really appreciate that the comment section has rewarded you both precisely equally.

Neel Nanda @ 2024-12-13T11:18 (+7)

I've only upvoted Habryka , to reward good formatting

Habryka @ 2024-12-12T21:38 (+5)

But I was first! I demand the moderators transfer all of the karma of Jeff's comment to mine :P 

Accolades for intellectual achievements by tradition go to the person who published them first.

Nathan Young @ 2024-12-15T09:38 (+7)

Sure, but surely we give it according to Shapley values? What if you had missed this? We should reward Jeff for that.

NunoSempere @ 2024-12-16T23:42 (+12)

Interesting that Robin Hanson brought this up 14 years ago.