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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

by fergie 1y ago

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?

ulrikrasmussen 1y 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.
fabian2k 1y 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.
solid_fuel 1y 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.
- duskwuff 1y ago
  Seconding this. I think my high school AP Biology class did a similar exercise in the early 2000s.
- mrheosuper 1y 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
  - fabian2k 1y 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.
  - solid_fuel 1y 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.
sjducb 1y 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.
- api 1y ago
  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!
- grumpy-de-sre 1y 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]. 1. http://en.wikipedia.org/wiki/Antibiotic_use_in_livestock http://en.wikipedia.org/wiki/Antibiotic_use_in_livestock 2. https://www.youtube.com/watch?v=6eaTIe_TBZA https://www.youtube.com/watch?v=6eaTIe_TBZA

by fergie 1y ago

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?

ulrikrasmussen 1y 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.

fabian2k 1y 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.

solid_fuel 1y 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.

duskwuff 1y ago
Seconding this. I think my high school AP Biology class did a similar exercise in the early 2000s.
mrheosuper 1y 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
- fabian2k 1y 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.
- solid_fuel 1y 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.

sjducb 1y 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.

api 1y ago
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!
grumpy-de-sre 1y 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]. 1. http://en.wikipedia.org/wiki/Antibiotic_use_in_livestock http://en.wikipedia.org/wiki/Antibiotic_use_in_livestock 2. https://www.youtube.com/watch?v=6eaTIe_TBZA https://www.youtube.com/watch?v=6eaTIe_TBZA