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Whenever this topic comes up on HN it strikes me as bizarre that anyone thinks they can genetically modify a bacteria, release it into the wild - and that it'll

Whenever this topic comes up on HN it strikes me as bizarre that anyone thinks they can genetically modify a bacteria, release it into the wild - and that it'll stay genetically modified? Like the author mentions, bacteria are constantly swapping genes via horizontal gene transfer. Surely the bacteria in our mouths have found the optimal metabolism for their environment? Why wouldn't we expect our genetically modified bacteria to adopt the same strategy? I imagine that you could, at least on paper, create a Rube Goldberg machine in their genes that, say, killed them if they produced lactic acid, and made it very difficult to delete these genes without destroying their ability to reproduce. But you'll probably also handicap them in the process and make it difficult for them to adapt to competitive adaptations from other bacteria.

ravenstine 2y ago
It's as if most of us don't have a background in biology or genetics.
- maxbond 2y ago
  Fair enough but I do feel like our everyday experience with biology informs this. If you cultivate a certain color of rose and release it into the wild, you wouldn't expect that color to persist, right? Maybe I'm out of touch but I feel like that's intuitive. Maybe the technology is sexy and dazzling and that makes it more difficult to engage critically.
  - ceejayoz 2y ago
    Depends on the plant. I've got two GMO plants in my house right now; glow-in-the-dark petunias (https://light.bio/ https://light.bio/) and purple tomatoes (https://www.norfolkhealthyproduce.com/ https://www.norfolkhealthyproduce.com/). The tomatoes breed true (i.e. the seeds have the gene); the petunias do not and must be cloned via propagation. Roses, fruit trees, etc. are the latter.
    - SamBam 2y ago
      The tomatoes will only breed true so long as they are hand-bred or kept in an environment where no other types of tomatoes are around. And even then mutations will eventually creep in. Same goes with the bacteria, except you may be talking about days or weeks instead of years.
      - ceejayoz 2y ago
        Tomatoes are largely self-polinating. Yes, mutations will creep in, but the gene will persist more based on a) can it be passed down to seeds and b) does it infer an advantage in natural selection?
        SamBam 2y ago
        The vast majority of changes made by humans to food plants, mostly through selective breeding, but also through gene editing, do not infer a selective advantage (except toward more human breeding). Big red fat juicy tomatoes are a disadvantage in the wild, where hundreds of thousands of years of natural selection pre-humans produced small, hardy, efficient, easy to maintain fruits. Just like with pure-bred dogs, if humans suddenly disappeared it would probably only take a few decades for many species to return to muttier wildtypes. Sure, some gene-editing is to make the plants hardier. Some of those genes would likely remain. We're getting rather off-topic, though, which is about whether the bacteria in your mouth would be likely to mutate and/or swap genes with other bacteria in your mouth.
    - maxbond 2y ago
      But those aren't really in the wild, right? They're in your garden? If they were left to their own devices and started to breed with wild type tomatoes, and/or were subject to selective pressures for an extended period, they probably would either abandon the gene or discover a niche it was adaptive for? Glow in the dark petunias sound really cool, I want those.
      - ceejayoz 2y ago
        The point is the gene may or may not be passed down at all. It's possible my glowing petunia has some sort of advantage - the energy use going into the light might be balanced by attracting bugs at night, perhaps - but its seeds won't ever have the adaptation. The purple tomato, on the other hand, if more attractive to birds who might eat and spread its seeds, might have more likelihood to spread.
  - blacksmith_tb 2y ago
    It's possible (in a sense the species we see were all the winners of the same process). And it's being proposed to try and push desired traits throughout populations, like disease-spreading mosquitos[1] 1: https://en.wikipedia.org/wiki/Gene_drive https://en.wikipedia.org/wiki/Gene_drive
dmbche 2y ago
You remind me - wasn't Crispr going to cure Malaria by modifying mosquitoes and releasing them in the wild? Wonder how thats going.
- grahamplace 2y ago
  Gene driving is the specific technique you’re referring to: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10795774/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10795774/
- ceejayoz 2y ago
  That's a technique used since the 1950s with great success against the parasitic screw-worm; it's now gone from North and Central America. Every year we release millions to keep them in South America. https://en.wikipedia.org/wiki/Sterile_insect_technique https://en.wikipedia.org/wiki/Sterile_insect_technique https://www.fao.org/4/u4220t/u4220T0g.htm https://www.fao.org/4/u4220t/u4220T0g.htm > In February 1991, after 15 years of production and the sterilization of 220 billion insects, Mexico was declared screwworm free. The screwworm rearing plant in Mexico, the only one of its kind, continues producing flies on a large scale for the eradication efforts under way in Central America and now provides FAO's Screwworm Emergency Centre for North Africa (SECNA) with sterile flies to combat the recent outbreak in North Africa.
  - dmbche 2y ago
    Incredible! Thanks for the link.
aspectmin 2y ago
>Whenever this topic comes up on HN it strikes me as bizarre that anyone thinks they can genetically modify a bacteria, release it into the wild - and that it'll stay genetically modified? Hubris? I'm all for progress and innovation. We need to couch such progress through the lens of thinking through the potential impacts of such progress though.
- somenameforme 2y ago
  $$$ is a much easier explanation. People selling things that they know won't work in the way they claim is as old as time. Never attribute to incompetence that which can be attributed to malice, when it involves earning a ton of money.
pragma_x 2y ago
> and that it'll stay genetically modified? I honestly think the play here is to have customers continually inoculate with the same, or even improved, versions of their modified bacteria. Possibly with a very strong antibiotic course in between if a clean slate is needed. That would provide ample room to stay on top of mutations and gene swapping in-situ. Otherwise, you don't have a continuous revenue model or a successful product.
- SamBam 2y ago
  But how do your re-inoculations colonize the teeth that have been fully colonized by your now-mutated old strains? Is the plan to require a full antibiotic mouthwash every few days, and then fresh inoculation? Ugh.
- twic 2y ago
  Or just brush your teeth twice a day.
  - SamPatt 2y ago
    Seriously - this is interesting tech but it seems like a mostly solved problem. Brush your teeth when you wake up, then floss and brush them again before you sleep. Once it's routine (hopefully established in youth) it seems extremely easy to maintain.
    - ToValueFunfetti 2y ago
      It's evidently not a solved problem- 80% of Americans have had a cavity by their mid thirties. I very much doubt even 5% of them were never told to brush their teeth.
      - hhjinks 2y ago
        Then on the other hand, a dingle cavity isn't a big deal, and might be enough to scare people into better oral hygiene. It did for me, at least.
  - 2y ago
swatcoder 2y ago
There are obviously numerous locally-optimal strategies for bacterial colonies in one's mouth (and gut, etc) as the population of bacteria varies widely across individual people. That's not to suggest that knocking out one or two specific functions is going to accomplish recolonization, or that we should even trust the effort to be wise in the medium-/long-term in light of gene transfer or migration into the gut and elsewhere, but the broad idea of pursuing recolonization by less destructive bacteria isn't without merit in itself.
teeray 2y ago
> I imagine that you could, at least on paper, create a Rube Goldberg machine in their genes that, say, killed them if they produced lactic acid It’s like Jurassic Park’s “Lysine Contingency”, but in your mouth
- Terr_ 2y ago
  In this case it sounds more like the dinosaurs would have a fatal allergy to human flesh.
- brookst 2y ago
  I do not think "Jurassic Park, but in your mouth" is a winning marketing angle.
  - red-iron-pine 2y ago
    disagree, i think that's a hilarious line and will get eyeballs / thoughts
polishdude20 2y ago
On that note, I wonder how kissing affects our mouth bacteria. Like, does making out with someone transfer enough bacteria between the two people to make a difference?
- evmar 2y ago
  Babies are born without the mouth bacteria that cause cavities, and generally acquire them from their parents (e.g. kissing or sharing utensils).
  - Tagbert 2y ago
    Or transmitting prechewed food. That's the old school way.
- 0x457 2y ago
  Not sure about just kissing, but here is about couples living together: https://journals.asm.org/doi/10.1128/msystems.00043-17 https://journals.asm.org/doi/10.1128/msystems.00043-17 I have a friend who started having a lot of teeth issues after moving in together. She swears nothing else has changed (i.e. food or stuff)
worik 2y ago
> ...create a Rube Goldberg machine in their genes that, say, killed them.. Bacteria are not machines, DNA is node code. Life is very different from mechanics
- pas 2y ago
  it's awfully close though https://berthub.eu/articles/posts/reverse-engineering-source-code-of-the-biontech-pfizer-vaccine/ https://berthub.eu/articles/posts/reverse-engineering-source...
- maxbond 2y ago
  You can, however, build machines using genes. Eg I met someone who was working on research to come up with sets of genes that implemented low level programming primitives, like "if". When some chemical concentration reaches a certain level, a gene is turned on or off. This is fundamental to how cells work, they're just trying to repurpose the machinery that's already there (if you'll forgive the metaphor). The research I've heard of that I was thinking about here was about splicing genes in such a way that in order to remove it, you will also need to remove genes necessary for reproduction. I'm not a geneticist and it's been a long time since I've read about this type of thing, so if I'm mistaken or if you know more, I'm all ears.

ravenstine 2y ago

It's as if most of us don't have a background in biology or genetics.

maxbond 2y ago
Fair enough but I do feel like our everyday experience with biology informs this. If you cultivate a certain color of rose and release it into the wild, you wouldn't expect that color to persist, right? Maybe I'm out of touch but I feel like that's intuitive. Maybe the technology is sexy and dazzling and that makes it more difficult to engage critically.
- ceejayoz 2y ago
  Depends on the plant. I've got two GMO plants in my house right now; glow-in-the-dark petunias (https://light.bio/ https://light.bio/) and purple tomatoes (https://www.norfolkhealthyproduce.com/ https://www.norfolkhealthyproduce.com/). The tomatoes breed true (i.e. the seeds have the gene); the petunias do not and must be cloned via propagation. Roses, fruit trees, etc. are the latter.
  - SamBam 2y ago
    The tomatoes will only breed true so long as they are hand-bred or kept in an environment where no other types of tomatoes are around. And even then mutations will eventually creep in. Same goes with the bacteria, except you may be talking about days or weeks instead of years.
    - ceejayoz 2y ago
      Tomatoes are largely self-polinating. Yes, mutations will creep in, but the gene will persist more based on a) can it be passed down to seeds and b) does it infer an advantage in natural selection?
      - SamBam 2y ago
        The vast majority of changes made by humans to food plants, mostly through selective breeding, but also through gene editing, do not infer a selective advantage (except toward more human breeding). Big red fat juicy tomatoes are a disadvantage in the wild, where hundreds of thousands of years of natural selection pre-humans produced small, hardy, efficient, easy to maintain fruits. Just like with pure-bred dogs, if humans suddenly disappeared it would probably only take a few decades for many species to return to muttier wildtypes. Sure, some gene-editing is to make the plants hardier. Some of those genes would likely remain. We're getting rather off-topic, though, which is about whether the bacteria in your mouth would be likely to mutate and/or swap genes with other bacteria in your mouth.
  - maxbond 2y ago
    But those aren't really in the wild, right? They're in your garden? If they were left to their own devices and started to breed with wild type tomatoes, and/or were subject to selective pressures for an extended period, they probably would either abandon the gene or discover a niche it was adaptive for? Glow in the dark petunias sound really cool, I want those.
    - ceejayoz 2y ago
      The point is the gene may or may not be passed down at all. It's possible my glowing petunia has some sort of advantage - the energy use going into the light might be balanced by attracting bugs at night, perhaps - but its seeds won't ever have the adaptation. The purple tomato, on the other hand, if more attractive to birds who might eat and spread its seeds, might have more likelihood to spread.
- blacksmith_tb 2y ago
  It's possible (in a sense the species we see were all the winners of the same process). And it's being proposed to try and push desired traits throughout populations, like disease-spreading mosquitos[1] 1: https://en.wikipedia.org/wiki/Gene_drive https://en.wikipedia.org/wiki/Gene_drive

dmbche 2y ago

You remind me - wasn't Crispr going to cure Malaria by modifying mosquitoes and releasing them in the wild? Wonder how thats going.

grahamplace 2y ago
Gene driving is the specific technique you’re referring to: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10795774/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10795774/
ceejayoz 2y ago
That's a technique used since the 1950s with great success against the parasitic screw-worm; it's now gone from North and Central America. Every year we release millions to keep them in South America. https://en.wikipedia.org/wiki/Sterile_insect_technique https://en.wikipedia.org/wiki/Sterile_insect_technique https://www.fao.org/4/u4220t/u4220T0g.htm https://www.fao.org/4/u4220t/u4220T0g.htm > In February 1991, after 15 years of production and the sterilization of 220 billion insects, Mexico was declared screwworm free. The screwworm rearing plant in Mexico, the only one of its kind, continues producing flies on a large scale for the eradication efforts under way in Central America and now provides FAO's Screwworm Emergency Centre for North Africa (SECNA) with sterile flies to combat the recent outbreak in North Africa.
- dmbche 2y ago
  Incredible! Thanks for the link.

aspectmin 2y ago

>Whenever this topic comes up on HN it strikes me as bizarre that anyone thinks they can genetically modify a bacteria, release it into the wild - and that it'll stay genetically modified? Hubris? I'm all for progress and innovation. We need to couch such progress through the lens of thinking through the potential impacts of such progress though.

somenameforme 2y ago
$$$ is a much easier explanation. People selling things that they know won't work in the way they claim is as old as time. Never attribute to incompetence that which can be attributed to malice, when it involves earning a ton of money.

pragma_x 2y ago

> and that it'll stay genetically modified? I honestly think the play here is to have customers continually inoculate with the same, or even improved, versions of their modified bacteria. Possibly with a very strong antibiotic course in between if a clean slate is needed. That would provide ample room to stay on top of mutations and gene swapping in-situ. Otherwise, you don't have a continuous revenue model or a successful product.

SamBam 2y ago
But how do your re-inoculations colonize the teeth that have been fully colonized by your now-mutated old strains? Is the plan to require a full antibiotic mouthwash every few days, and then fresh inoculation? Ugh.
twic 2y ago
Or just brush your teeth twice a day.
- SamPatt 2y ago
  Seriously - this is interesting tech but it seems like a mostly solved problem. Brush your teeth when you wake up, then floss and brush them again before you sleep. Once it's routine (hopefully established in youth) it seems extremely easy to maintain.
  - ToValueFunfetti 2y ago
    It's evidently not a solved problem- 80% of Americans have had a cavity by their mid thirties. I very much doubt even 5% of them were never told to brush their teeth.
    - hhjinks 2y ago
      Then on the other hand, a dingle cavity isn't a big deal, and might be enough to scare people into better oral hygiene. It did for me, at least.
- 2y ago

swatcoder 2y ago

There are obviously numerous locally-optimal strategies for bacterial colonies in one's mouth (and gut, etc) as the population of bacteria varies widely across individual people. That's not to suggest that knocking out one or two specific functions is going to accomplish recolonization, or that we should even trust the effort to be wise in the medium-/long-term in light of gene transfer or migration into the gut and elsewhere, but the broad idea of pursuing recolonization by less destructive bacteria isn't without merit in itself.

teeray 2y ago

> I imagine that you could, at least on paper, create a Rube Goldberg machine in their genes that, say, killed them if they produced lactic acid It’s like Jurassic Park’s “Lysine Contingency”, but in your mouth

Terr_ 2y ago
In this case it sounds more like the dinosaurs would have a fatal allergy to human flesh.
brookst 2y ago
I do not think "Jurassic Park, but in your mouth" is a winning marketing angle.
- red-iron-pine 2y ago
  disagree, i think that's a hilarious line and will get eyeballs / thoughts

polishdude20 2y ago

On that note, I wonder how kissing affects our mouth bacteria. Like, does making out with someone transfer enough bacteria between the two people to make a difference?

evmar 2y ago
Babies are born without the mouth bacteria that cause cavities, and generally acquire them from their parents (e.g. kissing or sharing utensils).
- Tagbert 2y ago
  Or transmitting prechewed food. That's the old school way.
0x457 2y ago
Not sure about just kissing, but here is about couples living together: https://journals.asm.org/doi/10.1128/msystems.00043-17 https://journals.asm.org/doi/10.1128/msystems.00043-17 I have a friend who started having a lot of teeth issues after moving in together. She swears nothing else has changed (i.e. food or stuff)

worik 2y ago

> ...create a Rube Goldberg machine in their genes that, say, killed them.. Bacteria are not machines, DNA is node code. Life is very different from mechanics

pas 2y ago
it's awfully close though https://berthub.eu/articles/posts/reverse-engineering-source-code-of-the-biontech-pfizer-vaccine/ https://berthub.eu/articles/posts/reverse-engineering-source...
maxbond 2y ago
You can, however, build machines using genes. Eg I met someone who was working on research to come up with sets of genes that implemented low level programming primitives, like "if". When some chemical concentration reaches a certain level, a gene is turned on or off. This is fundamental to how cells work, they're just trying to repurpose the machinery that's already there (if you'll forgive the metaphor). The research I've heard of that I was thinking about here was about splicing genes in such a way that in order to remove it, you will also need to remove genes necessary for reproduction. I'm not a geneticist and it's been a long time since I've read about this type of thing, so if I'm mistaken or if you know more, I'm all ears.