If what they are describing (marking strains using kanamycin) and creating deletion mutants really is what the NIH now considers gain-of-function research (nevermind dangerous) then all microbiology research has to stop immediately.
pazimzadeh 1 hours ago [-]
*kanamycin resistance cassette
timschmidt 37 minutes ago [-]
There's some debate in these comments about the origins of Covid, so I figured it'd be worth dropping the following testimony on the topic which I found eye opening:
To me, a total outsider, developing antibiotic resistant strains of TB sounds at least "gain of function"-adjacent. Are there any experts here who would like to hazard a judgement?
solid_fuel 2 hours ago [-]
I did this kind of work in a community college biotech program (literally biotech 102, we used E. Coli just to learn the technique). They are not engineering a new, deadlier strain of bacteria, they are using antibiotic resistance to solve a very simple problem: genetic modification is a probabilistic process, you have Gene A and need to get it into bacteria, but Gene A doesn't make the bacteria different externally in any easily detectable way.
So, after the process of inserting Gene A into a batch of bacteria you need to figure out which of the bacteria actually picked up Gene A so you can proceed to the next step of your experiment. So, what you do is you pair Gene A with Gene B, which is a very light resistance to a very specific antibiotic. Now, after you perform the electroporation, you plate the bacteria on agarose gel, let colonies start to develop, and then lightly dose the gel with the antibiotic.
The surviving bacterial colonies are those which have incorporated both Gene A and Gene B (because they are paired). It's just a way of filtering bacteria after electroporation so you can do further work. It's not dangerous to people because A) this antibiotic resistance was already found in nature, B) it's a resistance to a very specific antibiotic, not all antibiotics, and C) you're doing this in a protected lab.
This is an incredibly standard process, to the point where - again - I did this in a Biotech 102 program at community college. You could sign up for a classes where you learn to do this, right now.
mrheosuper 1 hours ago [-]
Interesting.
I have a question, why not pair Gene A with something still detectable but less "dangerous", like a gene that change body color, or emit different color under UV light.
Sorry i am totally noob here
solid_fuel 20 minutes ago [-]
Just to elaborate a bit more, the problem is that even a colony which, for example, glows under a blue light, will have some members that didn't uptake the genes. So you need a more proactive filtering method.
There's also the fact that bacteria tend to lose non-adaptive traits pretty quickly once the selection pressure is gone, so having the antibiotic resistance attached to your gene of interest makes it much more likely to stick around for the duration.
Additionally, as others have said, this particular antibiotic (from the post) isn't even used for human treatment so it's not really particularly more "dangerous", we just tend to get nervous around anything "antibiotic resistant" because we jump to thinking about like, MRSA.
fabian2k 55 minutes ago [-]
Because the antibiotic automatically selects the successful clones. The others that didn't incorporate the plasmid don't grow into colonies. Without antibiotics your plate will be entirely full of bacteria, you can't pick individual clones from that.
And you want clones, so all identical bacteria derived from a single successful integration of your plasmid into a bacterium. You don't want a mixture of bacteria with different DNA. This process isn't perfect and you need to screen out cases where your DNA sequence is not correct. And by far the easiest way to do that is to grow on plates with antibiotics, and an amount of bacteria that results in a few individual colonies, with each clone being full of genetically identical bacteria.
You generally want antibiotics in your media anyway, working without antibiotics makes it much more difficult. You don't have 100% perfectly sterile conditions, with antibiotics you have a much larger margin here.
duskwuff 1 hours ago [-]
Seconding this. I think my high school AP Biology class did a similar exercise in the early 2000s.
gwd 1 hours ago [-]
> A) this antibiotic resistance was already found in nature, B) it's a resistance to a very specific antibiotic, not all antibiotics
These are reasonable, but...
> C) you're doing this in a protected lab.
...this one is problematic. It's not taking the concerns of the people you're talking to seriously; namely, that no lab can be protected enough, that there's always a chance of leaking, and that the more GoF research is done the higher chance something is going to leak.
If nothing else, not registering that you even understand someone's concern is a sure-fire way to get them to ignore everything else you say.
And, I'm not sure exactly what your attitude is, but at least the way you put it here does sound overconfident. Sure, protocols should be safe if they're all followed; but the protocols are followed by people, and people make mistakes. Just take a look at all the nuclear accidents that have happened in spite of protocols.
Your best bet, I think, would be to lean on A and B: "There are strict protocols in place around labs to keep things from leaking; but even in the very unlikely event that something like this does leak, it won't really have any impact: as I said, the antibiotic resistance is a mutation that evolved by itself in the wild already; it won't make things worse than they already are."
EDIT: Or, at least, to say: "Look, I know it sounds really scary, but if you'd seen the protocols, you see how basically impossible they are to screw up. <brief descripiton of why it's unlikely to leak even if implemented by lazy or incompetent people.>"
The point is to let people know that you hear and understand their concern, and then to educate them about why their concern is unfounded.
actionfromafar 30 minutes ago [-]
You know some labs with active bioreactors which aren't protected at all? And the waste just dumped into nature... Pigs and cows fed antiobiotics.
gwd 11 minutes ago [-]
I mean, yeah, add that in there.
Listen, I'm not trying to argue that the containment protocols aren't safe; I don't know what they are. What I am trying to argue is
1. That these fears are reasonable, and deserve to be treated with respect.
2. Even if you don't agree with #1, in a democracy, just insulting and ignoring people with those fears is going to be counterproductive.
fragmede 11 minutes ago [-]
You don't get it! I watched 28 days later as a child and got really scared, and now nobody should ever do any biological research never again.
sjducb 1 hours ago [-]
Biologists modify cells so that we can study them. The modifications are about 0.00001% effective. If you attempt to modify 10^6 cells then maybe 20 cells will be modified. Most cells do not take the modification. So you need to select out the individual cells that have been modified.
You do this by including antibiotic resistance genes alongside your modification. Now all modified cells are resistant to the antibiotic. Then you apply a small amount antibiotic to kill the unmodified cells. Now you only have the cells with your interesting modification.
This is the mainstay of molecular biology. Every lab biologist has done it. We even do it as college students in lab practicals.
Banning the use of antibiotic resistance genes in biological research is effectively banning all wet lab medical research.
grumpy-de-sre 38 minutes ago [-]
I always thought it was only a matter of time before the general public heard the term "antibiotic resistance" and had a freak out.
Conveniently ignoring the fact that they're literally feeding the stuff to livestock to improve growth rates / feed efficiency [1]. Talk about dangerous gain-of-function "research". Industrial vat grown protein cannot come soon enough [2].
The entire biology field is filled with terrorists! We had no idea! I bet they also use 5G radiation to make the chemtrails! Ban dihydrogen monoxide!
fabian2k 2 hours ago [-]
As the article states, it is technically a gain of function experiment. But what is actually prohibited are dangerous gain of function experiments.
This specific use of antibiotics resistance is also extremely common. Pretty much every single microbiology experiment starts this way, and every time you want to genetically modify bacteria you do this. This includes every time you want to produce any protein, because you need genetically modified bacteria for that. This is a large part of all labwork in this field.
As the article notes, the antiobiotic used is one that isn't used for humans. So there is not significant additional danger due to that modification. The bacterium itself is much more dangerous than most that are handled in the lab, but that's why they're in a BSL-3 lab.
ulrikrasmussen 2 hours ago [-]
I thought the point of the article was that it was indeed adjacent, but that in their particular case there was no risk because (1) the mutated bacteria are actually less virulent, and (2) the mutated bacteria are resistant to one particular type of antibiotic which is not in use due to safety issues, but they are not resistant to any of the drugs that are actually used in humans to treat TB.
kedihacker 3 hours ago [-]
Well letting tb evolve over time and infect everyone is a lot more dangerous
yeahrightthere 3 hours ago [-]
[flagged]
tentacleuno 3 hours ago [-]
Has that ever been proved? All sources I can find are riddled in ambiguity. It's "one of two scenarios". I suppose we'll never really know for certain.
solid_fuel 1 hours ago [-]
It has never been proven, it's just a conspiracy theory and a convenient way to blame China. The truth is that viruses are constantly evolving in nature, and pandemics are a fairly regular occurrence as a result.
throwawayqqq11 3 hours ago [-]
Even if it was true:
1) It would be lacking bio safety, not GoF research. There are plenty of dangerous viruses stored away for research, which could escape too. Would you like to ban storage aswell?
2) Viruses mutate even if we stop GoF research. So why not try to stay ahead of the curve.
3) Many people died because conspiracy fueled rejection from vaccines even up to masks. Or would you like to elaborate how many millions died because of the new mRNA vaccine?
SilverElfin 2 hours ago [-]
Reminder that the Obama administration banned gain of function research due to its dangers. Only for Fauci to perform it through EcoHealth and WIV while claiming he’s not funding it.
Quarrel 40 minutes ago [-]
They paused funding actual dangerous gain-of-function (as the article makes the distinction), while developing new guidelines for how it should be managed.
They then released the new framework of multi-layered review to clearly define the tradeoffs and how they were managed, and resumed funding for those that could meet the improved criteria.
ie it was standard research advancing regulatory risk management.
chaostheory 3 hours ago [-]
Because gain of function research is dangerous. It’s also what likely turned Covid into a pandemic.
The article explains pretty well why this particular research isn't dangerous. It's technically gain of function, but if you prohibit any research that adds antibiotic resistance to bacteria you eliminated essentially all of microbiology research.
polotics 2 hours ago [-]
Both of the article's technique can much better be described as "removal-of-function" research IMHO.
solid_fuel 17 minutes ago [-]
Someone compiled a virus, compilation is dangerous, let's ban compilers.
JV00 3 hours ago [-]
Perhaps it would be better to address the issues that can lead to an incident rather than stopping all research. Even counting the COVID-19 pandemic, the overall impact of gain-of-function research on health is still positive.
jbstack 3 hours ago [-]
Knives are dangerous if used dangerously. Let's ban knives.
jjgreen 1 hours ago [-]
Welcome to the UK.
hackingonempty 3 hours ago [-]
It is scary to see the President and Health Secretary and their appointees acting on conspiracy theories.
The evidence for zoonotic origin of SARS-COV2 is very strong[0] and the conspiracy theorists as usual have little more than speculation.
Great links and even briefly skimming them makes me lean more towards zoonosis myself.
However, @hackingonempty's comment shows how dangerous over politicising these topics can be. Claiming lab-accident origin as a conspiracy theory stifles debates like the one linked.
Take a report from the first link where experts in the field still give a 21% chance to lab leak definitely takes it out of the range of conspiracy theories.
The only reason it was "removed" as a plausible origin was politics.
> asked how likely it is that COVID-19 originated from natural zoonosis, experts gave an average likelihood of 77% (median=90%). In fact, four out of five experts stated that a natural zoonotic origin was more than 50% likely.
> However, consensus was not complete. Across all experts, the average likelihood they gave for a research-related accident origin was 21%. Overall, one out of five experts reported a 50% or greater chance for an origin other than natural zoonosis.
https://www.hsgac.senate.gov/wp-content/uploads/Testimony-Qu...
It references a great deal of information from https://project-evidence.github.io/
And I've found Jamie Metzl's collection of resources interesting as well: https://jamiemetzl.com/origins-of-sars-cov-2/
So, after the process of inserting Gene A into a batch of bacteria you need to figure out which of the bacteria actually picked up Gene A so you can proceed to the next step of your experiment. So, what you do is you pair Gene A with Gene B, which is a very light resistance to a very specific antibiotic. Now, after you perform the electroporation, you plate the bacteria on agarose gel, let colonies start to develop, and then lightly dose the gel with the antibiotic.
The surviving bacterial colonies are those which have incorporated both Gene A and Gene B (because they are paired). It's just a way of filtering bacteria after electroporation so you can do further work. It's not dangerous to people because A) this antibiotic resistance was already found in nature, B) it's a resistance to a very specific antibiotic, not all antibiotics, and C) you're doing this in a protected lab.
This is an incredibly standard process, to the point where - again - I did this in a Biotech 102 program at community college. You could sign up for a classes where you learn to do this, right now.
I have a question, why not pair Gene A with something still detectable but less "dangerous", like a gene that change body color, or emit different color under UV light.
Sorry i am totally noob here
There's also the fact that bacteria tend to lose non-adaptive traits pretty quickly once the selection pressure is gone, so having the antibiotic resistance attached to your gene of interest makes it much more likely to stick around for the duration.
Additionally, as others have said, this particular antibiotic (from the post) isn't even used for human treatment so it's not really particularly more "dangerous", we just tend to get nervous around anything "antibiotic resistant" because we jump to thinking about like, MRSA.
And you want clones, so all identical bacteria derived from a single successful integration of your plasmid into a bacterium. You don't want a mixture of bacteria with different DNA. This process isn't perfect and you need to screen out cases where your DNA sequence is not correct. And by far the easiest way to do that is to grow on plates with antibiotics, and an amount of bacteria that results in a few individual colonies, with each clone being full of genetically identical bacteria.
You generally want antibiotics in your media anyway, working without antibiotics makes it much more difficult. You don't have 100% perfectly sterile conditions, with antibiotics you have a much larger margin here.
These are reasonable, but...
> C) you're doing this in a protected lab.
...this one is problematic. It's not taking the concerns of the people you're talking to seriously; namely, that no lab can be protected enough, that there's always a chance of leaking, and that the more GoF research is done the higher chance something is going to leak.
If nothing else, not registering that you even understand someone's concern is a sure-fire way to get them to ignore everything else you say.
And, I'm not sure exactly what your attitude is, but at least the way you put it here does sound overconfident. Sure, protocols should be safe if they're all followed; but the protocols are followed by people, and people make mistakes. Just take a look at all the nuclear accidents that have happened in spite of protocols.
Your best bet, I think, would be to lean on A and B: "There are strict protocols in place around labs to keep things from leaking; but even in the very unlikely event that something like this does leak, it won't really have any impact: as I said, the antibiotic resistance is a mutation that evolved by itself in the wild already; it won't make things worse than they already are."
EDIT: Or, at least, to say: "Look, I know it sounds really scary, but if you'd seen the protocols, you see how basically impossible they are to screw up. <brief descripiton of why it's unlikely to leak even if implemented by lazy or incompetent people.>"
The point is to let people know that you hear and understand their concern, and then to educate them about why their concern is unfounded.
Listen, I'm not trying to argue that the containment protocols aren't safe; I don't know what they are. What I am trying to argue is
1. That these fears are reasonable, and deserve to be treated with respect.
2. Even if you don't agree with #1, in a democracy, just insulting and ignoring people with those fears is going to be counterproductive.
You do this by including antibiotic resistance genes alongside your modification. Now all modified cells are resistant to the antibiotic. Then you apply a small amount antibiotic to kill the unmodified cells. Now you only have the cells with your interesting modification.
This is the mainstay of molecular biology. Every lab biologist has done it. We even do it as college students in lab practicals.
Banning the use of antibiotic resistance genes in biological research is effectively banning all wet lab medical research.
Conveniently ignoring the fact that they're literally feeding the stuff to livestock to improve growth rates / feed efficiency [1]. Talk about dangerous gain-of-function "research". Industrial vat grown protein cannot come soon enough [2].
1. http://en.wikipedia.org/wiki/Antibiotic_use_in_livestock
2. https://www.youtube.com/watch?v=6eaTIe_TBZA
This specific use of antibiotics resistance is also extremely common. Pretty much every single microbiology experiment starts this way, and every time you want to genetically modify bacteria you do this. This includes every time you want to produce any protein, because you need genetically modified bacteria for that. This is a large part of all labwork in this field.
As the article notes, the antiobiotic used is one that isn't used for humans. So there is not significant additional danger due to that modification. The bacterium itself is much more dangerous than most that are handled in the lab, but that's why they're in a BSL-3 lab.
1) It would be lacking bio safety, not GoF research. There are plenty of dangerous viruses stored away for research, which could escape too. Would you like to ban storage aswell?
2) Viruses mutate even if we stop GoF research. So why not try to stay ahead of the curve.
3) Many people died because conspiracy fueled rejection from vaccines even up to masks. Or would you like to elaborate how many millions died because of the new mRNA vaccine?
They then released the new framework of multi-layered review to clearly define the tradeoffs and how they were managed, and resumed funding for those that could meet the improved criteria.
ie it was standard research advancing regulatory risk management.
https://www.sciencedirect.com/science/article/abs/pii/S07554...
https://www.newsweek.com/controversial-wuhan-lab-experiments...
https://www.newsweek.com/covid-lab-leak-china-virus-nuclear-...
https://www.vanityfair.com/news/2022/10/covid-origins-invest...
https://www.propublica.org/article/senate-report-covid-19-or...
https://onlinelibrary.wiley.com/doi/full/10.1002/bies.202000...
The evidence for zoonotic origin of SARS-COV2 is very strong[0] and the conspiracy theorists as usual have little more than speculation.
[0] https://www.annualreviews.org/content/journals/10.1146/annur...
https://www.astralcodexten.com/p/practically-a-book-review-r... https://www.astralcodexten.com/p/highlights-from-the-comment...
However, @hackingonempty's comment shows how dangerous over politicising these topics can be. Claiming lab-accident origin as a conspiracy theory stifles debates like the one linked.
Take a report from the first link where experts in the field still give a 21% chance to lab leak definitely takes it out of the range of conspiracy theories.
The only reason it was "removed" as a plausible origin was politics.
> asked how likely it is that COVID-19 originated from natural zoonosis, experts gave an average likelihood of 77% (median=90%). In fact, four out of five experts stated that a natural zoonotic origin was more than 50% likely. > However, consensus was not complete. Across all experts, the average likelihood they gave for a research-related accident origin was 21%. Overall, one out of five experts reported a 50% or greater chance for an origin other than natural zoonosis.