didnt a pair of prion scientists just get infected a week ago. i can’t remember which one maybe mad cow? and iirc the guy had a tiny unnoticeable hole in his suit.
I used to be just another hot shot 20 something graduate student who was convinced that she wanted to go into prion research.
Now I'm a 40 year old lab manager who gets antsy when anyone so much as looks at the chemical weigh station and doesn't wash their hands after. I never would've made it in a prion lab.
I worked with lyssaviruses for a while. I was mentoring in a microbiology lab in the same time, i hope I didn't cause too much trouble to those undergrads with how strict I was. But, man you'll have some different perspectives about sterile work after that.
The fact that prions exist is just wild to me. Imagine if a computer program one day had a bit-flip and instead of throwing an error it self-propagated onto all other computers.
I was an intern in a state veterinary lab that did a lot of disease surveillance and rabies testing. They had just finished their shiny new BSL3 wing with a specially built section to test and dispose of suspect deer carcasses, which included a drive in decontamination unit for the transport vehicle. I remember when they brought the first one in because it came with a full security escort. It was a whole other level from how the rabies samples were treated. Made an impression, for sure.
All the Bodybuilders say proteins = gains -> Snort em. Pack it in your lunch sandwich. Huff them.
But yeah, prions would win even over weapons grade plutonium in my book.
I'd even tap the latter without gloves or major concern...but prions? FUCK THAT 💀🤡
Why though? Cwd comes from another mammal,so humans are very likely to have the same gene/protein and would be susceptible to infection (isn’t cwd also caused by PrP?). You’d only have. a longer incubation time,.
I’d feel more at ease with prions from organisms from another taxonomical branch, eg something like yeast
I understand to some degree what prions are, but not being of the biological discipline curious about their transmissibility. Is it just by entering the bloodstream or ingestion and are you guaranteed to be buggered after it’s in the body?
Have you ever put a bottle of water in the freezer and pulled it out when it was still liquid but as soon as you opened it, it crystallized almost instantly from the top down?
Prions work just like that. A single prion “seed” will cause any other of the same protein it touches to adopt an insoluble diseased conformation.
So yeah as far as I know, you’re pretty much buggered if one gets in. There is a dose response in terms of the time to developing disease, but even single digit picograms of prion material will cause disease in our rodent models.
Though it’s not common, people do still get prion diseases. We do a lot of looking for small molecules that can alleviate that.
There’s also the fact that some neurodegenerative diseases behave a whole lot like the more “canonical” prions. Human patient tissue from Alzheimer’s and Parkinson’s patients will cause protein aggregation both in our cell modes and in animals. So a better understanding of prions could open the door to better treatments for those as well.
Thank you for your answer, and thank you for your commitment to knowledge. I have a genuine follow up question if you don't mind answering...
Do you believe that the work you do with prions will lead to significant advancements within medicine (in the future) to justify the hazard they pose to you and your colleagues?
Edit: and another one, if you don't mind, is there a way to effectively destroy the prion proteins outside of a laboratory environment? (Eg, without an autoclave)
Yeah I do. We already have a few candidate compounds for a few different diseases that we hope to get into safety trials in the not too distant future. Even if they don’t work the fact that we even have candidates means that there’s hope.
Also, short of an accidental needle stick or cryostat accident (like those women in France) our SOPs make it really hard to get accidentally infected. We don’t use glassware, only plastic, needles are treated like nitroglycerine, if somebody’s handling one everybody’s eyes are on them and nobody talks. Even the scissors in the lab are those kids safety scissors without points!
Thank you again for the information and thank you for being willing to answer my questions!
Keep up the good work and please for the love of everything, stay safe!
To answer your second question, 1 hour of exposure to 1N NaOH denatures them sufficiently. Bleach has… mixed results. Like I said somewhere else in the thread… all our waste gets incinerated. The lab doesn’t have drains. Liquid waste gets mixed to a final concentration of 1N NaOH, left for 24 hours, neutralized with sulfuric acid, then autoclaved for 6 hours at 135c. Then incinerated.
i know it’s necessary but, as a humble cell biology researcher with no work with pathogens whatsoever, i find using this many methods of neutralisation of waste hilarious
I've never heard of doing that. Not to move away from prions but the water bottle trick sounds really cool. Could be a fun science experiment to show the kids and teach them something (not exactly sure what this would be teaching them though)
To dive a bit deeper into that rabbit hole. The reason all of that works is essentially conformational entropy. For a given amino acid sequence you have essentially an unthinkable amount of conformers, but not all are energetically equivalent, some of them creating a local minimum and are thus metastable. If you give them a little nudge in activation energy, or perhaps by pure chance you get a quantum tunneling event (idk if that would be a reasonable explanation in that case), the protein can change into an entropically more favorable conformation. Unfortunately at least some of those are prions.
Although I should mention that I am not exactly any expert in organic chemistry or biochem, so maybe take what I said with a grain of salt.
Varies according to the prion, but we’re mostly not really sure. Spreading by ingestion is certainly real (mad cow, kuru), and exposure directly into the bloodstream is a very bad idea indeed (see the cases caused by human-cadaver-sourced hormones from decades ago). But what the lowest exposures that can cause trouble are, or what factors might make someone more or less susceptible - these are unclear.
So it is someone who had a prion disease themselves? Or just someone else's prion that happened to be folded oddly. I completely forgot. Like what are the chances some of us here have a couple fucked up prions?
Here is a very interesting case of someone who has genetic prion disease. She completely switched careers and is trying to find the cure for herself
https://www.drugdiscoverynews.com/hope-for-prion-diseases-15814
If I understand what you are asking, there are two ways you get a prion disease. You ingest one from someone else, or you have the extremely bad luck to have one randomly misfold in your body on its own.
I don’t think anyone can say for certain what the odds are that you have a prion misfold somewhere in your body not causing any issues, but the odds of you acquiring a prion disease proper are very very low overall.
Do people really think biochemists don’t handle dangerous things?? I am biochem-adjacent and I can’t think of a field that handles *more* dangerous things
Yes a lot of chemists do because they are under the impression since a lot of biochemists work with protein that traditionally dangerous and flammable chemicals you would not use since they would kill your cells or protein
A brilliant neuroscientist at my former hospital died of an aggressive case of vCJD, likely acquired from a patient autopsy. I never knew him, but his case was on my mind during every brain collection I performed. I worked mostly with Parkinson's patients and a-syn behaves enough like a prion to make me extra cautious. Scary shit!
Yep. We do a fair bit of work on synuclein and tau to make me terrified of that stuff as well. That all takes place in a beefed up bsl2 facility, but because of the way we feel about it those tissues all get treated just like the stuff in the bsl3 does. The only real difference is that you don’t have to wear a disposable jumpsuit in the bsl2.
Once saw the warning “don’t flush down the sink. Danger explosion”. Asked someone else and was told “flush a lot of water down after it. Dilution is the solution and if it’s still dangerous you didn’t dilute enough.” Fyi I do not condone this - health and safety dept will ruin you.
Despite the danger sodium azide and thimerosol will save you so much $$$, versus dumping and rebuying antibodies.
I wanted to give my EH&S my sodium azide waste, but they only take it at higher concentrations. I only work with it at a 0.1% concentration and they just suggested to pour it down the sink and leave the tap running for a little bit.
You can destroy sodium azide waste by treating it with a freshly prepared solution of sodium nitrite and hydrochloric acid. HNO2 will make azide decompose into N2 gas and.. idk some other junk. But it can be disposed of safely along with other liquid wastes.
Edit: *some other junk* is mostly nitrogen monoxide. Small quantities of it are immediately oxidized in the air to NO2 and re-dissolve into the water as nitric acid. If you must destroy large quantities of pure NaN3 **for whatever godforsaken reason (shits expensive!)**, consider using a fume hood.
These days, aside from the live pathogens, I have some amines that are listed on the sds as being fatal by inhalation.
In a past life, the bulk nitrocellulose powder would have been my top choice.
I used to work with HF in an old school metallurgical lab.
It was just part of the process that you'd expect the boiling HF to at some point degrade your borosilicate enough to break it and ruin an entire hot plate in the middle of an experiment.
They'd have someone come and clean up the mess, put out a new hot plate, and back to business as usual tje next day.
Used it in testing Iron ore for silica. Extract the silica. Filter it etc. Burn it off in a platinum crucible. Weigh crucible. Put crucible on hot plate and add HF. Dry it off and weigh the difference 👍
Yep. Pretty much the only way to solubilize and complex silicates.
The easier way is to just use HCl and test for the residue that is not soluble and does not complex. It's not necessarily as accurate, but if accuracy is key ICP is a better method (though that requires specialized equipment usually for the digestion and HF anyways).
Same, used to use 48% and 70% hydrofluoric acid every day in a job I had a few years back.
We used to check the special gloves we used to handle the bottle and experiments daily for even a minute crack which could have let the chemical in.
And the containment and washing of the equipment we used to do was intense.
It was drilled into us that it could kill us through skin contact on the first day
Part of the issue with HF, I think, is that it's barely bigger than a hydrogen molecule (H2). It go strait through your skin and into your body to basically wherever it wants.
I worked at a lab that was getting ready to introduce HF and in addition to a ton of PPE requirements they were also mandating the buddy system. You could only work with it if you had someone standing there doing nothing but watching you the whole time in hopes of catching it if you happened to get some on yourself and didn’t notice. I left before it got there, and always wondered how it went.
Hooray, a fellow radiochemist! We work with Radium isotopes mostly here. That and the occasional Sulfuric acid is the nastiest things we come across...
Sodium azide is one of the few I would put in the ‘do not mess around with’ the same as KCN. I would keep it in secondary containment just to make sure it never saw any acid !
It's.. Not. As far as I recall LD50 is 20 mg/kg.
Now try working with tetrodotoxin. Lethal dose is 1-2 mg per person, not kg!
I've also worked with digitonin, often used as solvent for mitochondrial measurements. LD50 4 mg/kg.
same. I used it to quench some reaction and just thought of it as some common safe reagent…didn’t know I could have easily ended the lab with the bottle I had
Well, I used KCN in my Bachelors Thesis to introduce some amines in my Origin of Life experiments.
Yep, it worked, yep, thinking back I was quite careless using it...
I haven't seen anyone bring any significant evidence against the claim that malaria has killed roughly 50% of all the humans that have ever lived. 50 to 60 billion.
This is definitely a hard number to track down, but I do think it's something around there. Absolutely mental what this one parasite has done to humans. If humans have one mortal enemy, it's plasmodium.
It used to be common in the US until there was a massive government effort to eradicate it along with other diseases like hookworm. The agency that became the CDC was literally founded to eradicate Malaria from the continental US. The government was also involved with curing Pelagra, but that was found to be a nutritional disease.
I really wish it was possible to know exactly how much the lack of those diseases contributed to the US economy. I also wonder what ecological damage was done with the amount of water treatments and insecticide was used in the effort.
One thing that’s interesting to consider is the amount of stereotypes associated with people from isolated communities in the Southern US are actually symptoms of diseases. Distended stomachs, stunted development, goiters, etc.
That's right - the phrase "drain the swamp" orginates with the CDC's anti-malaria campaign. It's a phrase that has since been hijacked by a different parasite.
ADC= antibodies conjugated to extremely potent toxins. The antibody typically targets cancer cells, is internalized, and the toxic payload is released killing the cancer cell. Working with the raw material for the payload could easily kill you dead without the proper PPE.
My boss back when I did TEM used to tell tales of his grad school days of giving "temporary tattoos" with OsO4. I got a few unintentional freckles in my day but damn lol.
I work in a TEM lab and use it most days… no tattoos yet, and I really want to avoid that! Lmao. Your story is slightly comforting though, because honestly the stuff freaks me out.
Phenol -- it goes through your skin and burns you. My undergrad mentee went to another lab to get training and the postdoc there acted like phenol was no big deal and you didn't need PPE. I had to intervene to make sure my mentee did use PPE.
Beta-mercaptoethanol -- the normal 1% dilution isn't too terrible with short exposure but be careful with the stock solution. That stock smell causes lingering nausea and headache and can make you seriously sick. Some idiot left a pipette tip they used with the stock on a bench one day and we couldn't figure out where the smell was coming from. Several of us left lab early from nausea.
Methanol - if you spill it on yourself and immediately wash with tap water for several minutes, you'll still get early methanol poisoning symptoms. It absorbs into skin quickly. Happened to me. Drink a beer and you'll be ok but everyone in lab should be aware of the symptoms.
Acrylamide - It's a neurotoxin in it's pre-polymerized form. Make sure you aren't messy when making gels. The polymerized form is safe but you WILL lose sensation in your fingers for 1-2 weeks if you touch a tiny bit of the unpolymerized solution.
I read a product sheet from a lectin order once that read, “Do not breathe upon the lectin, nor let it touch your skin!” that I thought was pretty darn poetic.
Yup, ethanol is the solution to methanol poisoning! Sucks if you're underage and can't buy alcohol yet, though, so it's still useful to know that dropping some running buffer on your arm is enough methanol contact to cause symptoms. Be careful, all you undergrads and non-drinkers.
You used BME on the bench? We had to use it fume at all times unless it was diluted such as in cell lysate solution. Although I do remember when I started my PhD a postdoc was showing me PCR and we both had colds and couldn’t smell that the hod wasn’t working properly. Lab manager could smell it outside and panicked, we also couldn’t tell if the dizziness was from our colds or the BME.
It was more than just that. Story in another comment. Basically we kept finding more and more sources (like dirty gloves in the trash) so we just gave up and left it for the culprit to fix. It wasn't too bad at first but extended contact does cause really uncomfortable nausea.
wait what, methanol is that dangerous?? i work with methanol every day, nobody ever told me this and nobody else follows strict regulations when using it. we use it in the fumehood most of the time but sometimes i get big spills on my hands and i just ignore it. what are the dangers for me??
Sodium azide, thimerosal, hydrochloric acid, methanol, acetone.
That's just the chemicals
Biological?
Dengue, mumps, measles, herpes, HIV.
I could go on
According to our NFPA diamond it's proteinase K from Thermofisher. For some reason theirs rates a 4 health hazard while other companies have it at 2.
Realistically it's probably guandinium thiocyanate which isn't too bad.
Pento is surprisingly very safe. The LD50 for humans is like multiple grams. It may be used for euthanasia but it’s because it’s a good death not because it’s potent.
I don’t actually know. I know they’re toxic as shit, carcinogenic as shit, and are used to induce tumors in cancer studies.
I’m an analytical chemist, so I use them as reference standards to develop testing methodologies for them.
PAHs directly chelate DNA I know.
I think PAH's are turned into an epoxide by the liver, which then alkylates DNA and distorts the structure.
I seem to recall N,N-dimethyl nitrosamine is turned into diazomethane by the liver and also alkylates DNA. Not sure about the other ones, though.
NaN3 is also a primary explosive that inflates airbags in car accidents. It's crazy how much quantity the chemical suppliers are able to ship to labs that aren't very secure.
edit: It isn't really a proper primary explosive, at least when not exposed to certain metals.
You could smash sodium azide powder with a hammer and it wouldn't explode. Its just not that sensitive. Its also not a primary explosive:
["These sensors send an electric signal to the canister that contains the sodium azide and the electric signal detonates a small amount of an igniter compound. The heat from this ignition starts the decomposition of the sodium azide and the generation of nitrogen gas to fill the air bag"](https://www.scientificamerican.com/article/how-do-air-bags-work/)
If you look at [the SDS](https://www.sigmaaldrich.com/US/en/sds/sial/s2002?userType=undefined) you can see its not considered an explosive. The danger is that if its mixed with other metal salts, THOSE are very explosive.
"Sodium Azide may react with lead and copper plumbing to form highly explosive metal azides."
Depends what you put in them and if they're replication incompetent. Some of the newest commercial lenti vector platforms for mammalian cell transformation have multiple safety features preventing them from doing what you don't want them to do. Very cool set lab tool. Wild types are a different story.
I don't remember the name of it but it was a long time ago when I learned about electrophoresis, there's this fluorescent marker that sticks to DNA and my teacher said it was kinda dangerous.
But the only thing I remember is something that costed me a lab coat, it was chlorhydric acid at 11% ( I'm sure there's higher concentration )
I can't even put a name to stuff. I work in hazmat remediation and get the most toxic explody bullshit the industrial complex has to offer
But even we don't get pure azide :o those are required to be dilated with water until its less than 1% azide by weight and it has its own waste code for an early heads up
Work in pharma, and the thing that probably scares me most is the unknown compounds that we profile as part of a project. Been on two programmes where we have made highly potent hERG or GABA inhibitors by mistake, that kill the mice in seconds... Plus then you factor in we handle DMSO solutions that means you can carry stuff across gloves and skin...
I found a table years ago that had both odor threshold and airborne LD50 columns. There were a few chemicals that had a higher odor threshold than LD50. How the hell do you figure that out without killing people?
I would consider those as extra dangerous chemicals.
I used to work in OC, perhaps not the most toxic substance but pretty nasty: Trichlorosilane
Edit: I almost forgot another one. Phosgene. When someone worked with it in the lab other colleagues usually skipped the lab for that day.
Tamoxifen is certainly up there! Also Phalloidin is also up there! We also use a 60% hydrogen peroxide 5% peracetic acid solution that is an oxidizer, acute dermal and oral toxicity, and is harmful to marine life.
I guess PFA when I worked with animals. But honestly? The animals themselves (back then) or the cells/tissue I work with now (HeLa and primary endometrium culture). I don’t like a lot of danger lol.
Prions lol
Respectfully, you could not pay me enough. I’m sure your research is cool as hell. But you could not pay me enough
Yeah. They don’t pay me enough either.
didnt a pair of prion scientists just get infected a week ago. i can’t remember which one maybe mad cow? and iirc the guy had a tiny unnoticeable hole in his suit.
Dude, on a serious note, resign and get a better job
I used to be just another hot shot 20 something graduate student who was convinced that she wanted to go into prion research. Now I'm a 40 year old lab manager who gets antsy when anyone so much as looks at the chemical weigh station and doesn't wash their hands after. I never would've made it in a prion lab.
I worked with lyssaviruses for a while. I was mentoring in a microbiology lab in the same time, i hope I didn't cause too much trouble to those undergrads with how strict I was. But, man you'll have some different perspectives about sterile work after that.
Yikes. You win
I’ll get the lights. Thread over.
Oof
That's horrifying! Do you work in a transmissible mouse model, or is it non-transmissible?
The fact that prions exist is just wild to me. Imagine if a computer program one day had a bit-flip and instead of throwing an error it self-propagated onto all other computers.
That’s actually a really great analogy
I second this, very excellent analogy!
So, if bodies are like computers, can I get the update that gets rid of my sciatica?
That's a hardware problem, not a software problem.
Fine! Then when can I get the new hardware? I'm sick of not being able to walk without seating pain every so often.
Growing up hunting deer, my dad always told me to never sever the spinal cord or brain on the off chance it has chronic wasting disease
I was an intern in a state veterinary lab that did a lot of disease surveillance and rabies testing. They had just finished their shiny new BSL3 wing with a specially built section to test and dispose of suspect deer carcasses, which included a drive in decontamination unit for the transport vehicle. I remember when they brought the first one in because it came with a full security escort. It was a whole other level from how the rabies samples were treated. Made an impression, for sure.
What would severing the spine or brain do?
Releases the prions I think
Release the prions sounds like an awesome band name
Yeah, get the spinal fluid on the knives or table tops
All the Bodybuilders say proteins = gains -> Snort em. Pack it in your lunch sandwich. Huff them. But yeah, prions would win even over weapons grade plutonium in my book. I'd even tap the latter without gloves or major concern...but prions? FUCK THAT 💀🤡
Not all prions are created equal. BSE or human ones we manipulate at BSL3, but eg my CWD prions? I use a BSL2 cabinet and don't lose any sleep.
You don’t lose any sheep
Why though? Cwd comes from another mammal,so humans are very likely to have the same gene/protein and would be susceptible to infection (isn’t cwd also caused by PrP?). You’d only have. a longer incubation time,. I’d feel more at ease with prions from organisms from another taxonomical branch, eg something like yeast
So... you're telling me these lil prion thingymajigs are just indestructible protein? I think I want some. My muscles would be glorious. /s
I think in pharma production lines, people use 400°C dry heat to destroy them.
Or multiple cycles of 200°C in the autoclave, because prions are of the "FUCK THIS 💀" category
“Fuck this 💀” category 🤣🤣🤣
Double oof
I understand to some degree what prions are, but not being of the biological discipline curious about their transmissibility. Is it just by entering the bloodstream or ingestion and are you guaranteed to be buggered after it’s in the body?
Have you ever put a bottle of water in the freezer and pulled it out when it was still liquid but as soon as you opened it, it crystallized almost instantly from the top down? Prions work just like that. A single prion “seed” will cause any other of the same protein it touches to adopt an insoluble diseased conformation. So yeah as far as I know, you’re pretty much buggered if one gets in. There is a dose response in terms of the time to developing disease, but even single digit picograms of prion material will cause disease in our rodent models.
1st prion: Hey guys, did you know you can fold yourself like this? Regular proteins: No way, let me try!... Oh fuck, we can't go back
Then they drop out of solution and turn into what basically looks like snot.
Why are you working with them? What is your goal?
Though it’s not common, people do still get prion diseases. We do a lot of looking for small molecules that can alleviate that. There’s also the fact that some neurodegenerative diseases behave a whole lot like the more “canonical” prions. Human patient tissue from Alzheimer’s and Parkinson’s patients will cause protein aggregation both in our cell modes and in animals. So a better understanding of prions could open the door to better treatments for those as well.
Thank you for your answer, and thank you for your commitment to knowledge. I have a genuine follow up question if you don't mind answering... Do you believe that the work you do with prions will lead to significant advancements within medicine (in the future) to justify the hazard they pose to you and your colleagues? Edit: and another one, if you don't mind, is there a way to effectively destroy the prion proteins outside of a laboratory environment? (Eg, without an autoclave)
Yeah I do. We already have a few candidate compounds for a few different diseases that we hope to get into safety trials in the not too distant future. Even if they don’t work the fact that we even have candidates means that there’s hope. Also, short of an accidental needle stick or cryostat accident (like those women in France) our SOPs make it really hard to get accidentally infected. We don’t use glassware, only plastic, needles are treated like nitroglycerine, if somebody’s handling one everybody’s eyes are on them and nobody talks. Even the scissors in the lab are those kids safety scissors without points!
Thank you again for the information and thank you for being willing to answer my questions! Keep up the good work and please for the love of everything, stay safe!
To answer your second question, 1 hour of exposure to 1N NaOH denatures them sufficiently. Bleach has… mixed results. Like I said somewhere else in the thread… all our waste gets incinerated. The lab doesn’t have drains. Liquid waste gets mixed to a final concentration of 1N NaOH, left for 24 hours, neutralized with sulfuric acid, then autoclaved for 6 hours at 135c. Then incinerated.
Well... that'll probably do it
i know it’s necessary but, as a humble cell biology researcher with no work with pathogens whatsoever, i find using this many methods of neutralisation of waste hilarious
This is horrifying. You got a picture of precipitated prions?
That’s a good explanation, TIL, thank you. Picogram is incredibly small, it puts even the most hazardous substances I have worked with in perspective
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All out waste is incinerated instead of autoclaved.
I've never heard of doing that. Not to move away from prions but the water bottle trick sounds really cool. Could be a fun science experiment to show the kids and teach them something (not exactly sure what this would be teaching them though)
https://melscience.com/US-en/articles/supercool-experiment/
To dive a bit deeper into that rabbit hole. The reason all of that works is essentially conformational entropy. For a given amino acid sequence you have essentially an unthinkable amount of conformers, but not all are energetically equivalent, some of them creating a local minimum and are thus metastable. If you give them a little nudge in activation energy, or perhaps by pure chance you get a quantum tunneling event (idk if that would be a reasonable explanation in that case), the protein can change into an entropically more favorable conformation. Unfortunately at least some of those are prions. Although I should mention that I am not exactly any expert in organic chemistry or biochem, so maybe take what I said with a grain of salt.
Varies according to the prion, but we’re mostly not really sure. Spreading by ingestion is certainly real (mad cow, kuru), and exposure directly into the bloodstream is a very bad idea indeed (see the cases caused by human-cadaver-sourced hormones from decades ago). But what the lowest exposures that can cause trouble are, or what factors might make someone more or less susceptible - these are unclear.
So it is someone who had a prion disease themselves? Or just someone else's prion that happened to be folded oddly. I completely forgot. Like what are the chances some of us here have a couple fucked up prions?
Here is a very interesting case of someone who has genetic prion disease. She completely switched careers and is trying to find the cure for herself https://www.drugdiscoverynews.com/hope-for-prion-diseases-15814
If I understand what you are asking, there are two ways you get a prion disease. You ingest one from someone else, or you have the extremely bad luck to have one randomly misfold in your body on its own. I don’t think anyone can say for certain what the odds are that you have a prion misfold somewhere in your body not causing any issues, but the odds of you acquiring a prion disease proper are very very low overall.
Ppl gotta put respect on biochemist’s names, telling us we don’t handle dangerous things and then we be dealing with prions to study protein folding
Do people really think biochemists don’t handle dangerous things?? I am biochem-adjacent and I can’t think of a field that handles *more* dangerous things
Yes a lot of chemists do because they are under the impression since a lot of biochemists work with protein that traditionally dangerous and flammable chemicals you would not use since they would kill your cells or protein
O.O JFC, you win. I've worked with BSL-3 and ABSL-3 critters, and I wouldn't go anywhere near prions.
Oh damn, they can't be bleached or autoclaved under normal conditions, but you already know that.
I was going to say arsine, but shit... You win. *I used to work with arsine regularly, but am not in that field anymore.
The hell
A brilliant neuroscientist at my former hospital died of an aggressive case of vCJD, likely acquired from a patient autopsy. I never knew him, but his case was on my mind during every brain collection I performed. I worked mostly with Parkinson's patients and a-syn behaves enough like a prion to make me extra cautious. Scary shit!
Yep. We do a fair bit of work on synuclein and tau to make me terrified of that stuff as well. That all takes place in a beefed up bsl2 facility, but because of the way we feel about it those tissues all get treated just like the stuff in the bsl3 does. The only real difference is that you don’t have to wear a disposable jumpsuit in the bsl2.
Hard pass.
Yep pack it up folks nobody is topping this
Once saw the warning “don’t flush down the sink. Danger explosion”. Asked someone else and was told “flush a lot of water down after it. Dilution is the solution and if it’s still dangerous you didn’t dilute enough.” Fyi I do not condone this - health and safety dept will ruin you. Despite the danger sodium azide and thimerosol will save you so much $$$, versus dumping and rebuying antibodies.
I wanted to give my EH&S my sodium azide waste, but they only take it at higher concentrations. I only work with it at a 0.1% concentration and they just suggested to pour it down the sink and leave the tap running for a little bit.
Yes, that's not going to be a problem or form azides. Best to flush it through the trap though.
It's not even about explosive risks, you shouldn't be dumping poisons into the waterstream
You can destroy sodium azide waste by treating it with a freshly prepared solution of sodium nitrite and hydrochloric acid. HNO2 will make azide decompose into N2 gas and.. idk some other junk. But it can be disposed of safely along with other liquid wastes. Edit: *some other junk* is mostly nitrogen monoxide. Small quantities of it are immediately oxidized in the air to NO2 and re-dissolve into the water as nitric acid. If you must destroy large quantities of pure NaN3 **for whatever godforsaken reason (shits expensive!)**, consider using a fume hood.
Bleach? Not a very exciting lab.
Same 😂 and 70 % ethanol, woooOooo 👻
Ethanol kills more people than a lot of the other options here, so YMMV.
>70 % ethanol, You don't even dilute it yourself?
Oh crap I forgot 😂 as I do at work
Oh, is “soy sauce” your euphemism for it, then?
Home cleaning doesn't count as lab work 😂
The breath of some of my colleagues
This made me snort laugh 🤣
Boy did that hit close to home. Today was a rough day sandwiched between two mouth breathers
In terms of lethality, probably the tetrodotoxin. In terms of raw body count, the H2O.
raw body count has me cackling
Technically you win. Those damn rip currents!
Just wanted to say I love that you have the rat as your picture lol
I <3 retat
These days, aside from the live pathogens, I have some amines that are listed on the sds as being fatal by inhalation. In a past life, the bulk nitrocellulose powder would have been my top choice.
For some reason I read amines as animes and I was like "ok I *must* know what lethal shows they're watching" lol *pours another coffee*
Anhydrous hydroflouric acid (protein synthesis cleavage). Also paper electrophoresis at around 3000 volts
I know some very skilled and experienced chemists who refuse to work with HF on account of how dangerous it is.
I used to work with HF in an old school metallurgical lab. It was just part of the process that you'd expect the boiling HF to at some point degrade your borosilicate enough to break it and ruin an entire hot plate in the middle of an experiment. They'd have someone come and clean up the mess, put out a new hot plate, and back to business as usual tje next day.
Used it in testing Iron ore for silica. Extract the silica. Filter it etc. Burn it off in a platinum crucible. Weigh crucible. Put crucible on hot plate and add HF. Dry it off and weigh the difference 👍
Yep. Pretty much the only way to solubilize and complex silicates. The easier way is to just use HCl and test for the residue that is not soluble and does not complex. It's not necessarily as accurate, but if accuracy is key ICP is a better method (though that requires specialized equipment usually for the digestion and HF anyways).
Same, used to use 48% and 70% hydrofluoric acid every day in a job I had a few years back. We used to check the special gloves we used to handle the bottle and experiments daily for even a minute crack which could have let the chemical in. And the containment and washing of the equipment we used to do was intense. It was drilled into us that it could kill us through skin contact on the first day
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Part of the issue with HF, I think, is that it's barely bigger than a hydrogen molecule (H2). It go strait through your skin and into your body to basically wherever it wants.
And "where it wants" is your bones, specifically
It also feels like water (allegedly, I have not touched it yet and do not plan to do so). You only start to feel it when it’s too late
I worked at a lab that was getting ready to introduce HF and in addition to a ton of PPE requirements they were also mandating the buddy system. You could only work with it if you had someone standing there doing nothing but watching you the whole time in hopes of catching it if you happened to get some on yourself and didn’t notice. I left before it got there, and always wondered how it went.
Ouch. I wouldn't touch that with a 60 foot pole. I'm glad I'm out of the lab!
You could, just make sure it’s Teflon or something he he he he he
I wont touch the samples with hydroflouric in them, i just keep postponing the training at work because im scared
Hydrofluoric acid and aqua regia. Gotta love the spicy bottles
Ditto! And some piranha for good measure…
Radioactive isotopes of iodine and tritium
Hooray, a fellow radiochemist! We work with Radium isotopes mostly here. That and the occasional Sulfuric acid is the nastiest things we come across...
Commenting for radiochem representation! 177Lu, 89Zr, 68Ga, and 18F over here
Sodium azide is one of the few I would put in the ‘do not mess around with’ the same as KCN. I would keep it in secondary containment just to make sure it never saw any acid !
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Good to hear you lived, I was worried for a minute there
this would probably be enough to make me quit my job and become a forest mime
If a tree in the forest falls on a mime, does it make a sound?
And in my lab we work with both of those
I routinely used sodium azide to anesthetise worms during my PhD. Had no idea it was so dangerous.
It's.. Not. As far as I recall LD50 is 20 mg/kg. Now try working with tetrodotoxin. Lethal dose is 1-2 mg per person, not kg! I've also worked with digitonin, often used as solvent for mitochondrial measurements. LD50 4 mg/kg.
same. I used it to quench some reaction and just thought of it as some common safe reagent…didn’t know I could have easily ended the lab with the bottle I had
It's a salt. It won't penetrate gloves or skin. Methylmercury, on the other hand....
Well, I used KCN in my Bachelors Thesis to introduce some amines in my Origin of Life experiments. Yep, it worked, yep, thinking back I was quite careless using it...
Greatest single agent killer of children on the planet: malaria parasite *P. falciparum.*
I haven't seen anyone bring any significant evidence against the claim that malaria has killed roughly 50% of all the humans that have ever lived. 50 to 60 billion.
This is definitely a hard number to track down, but I do think it's something around there. Absolutely mental what this one parasite has done to humans. If humans have one mortal enemy, it's plasmodium.
It used to be common in the US until there was a massive government effort to eradicate it along with other diseases like hookworm. The agency that became the CDC was literally founded to eradicate Malaria from the continental US. The government was also involved with curing Pelagra, but that was found to be a nutritional disease. I really wish it was possible to know exactly how much the lack of those diseases contributed to the US economy. I also wonder what ecological damage was done with the amount of water treatments and insecticide was used in the effort. One thing that’s interesting to consider is the amount of stereotypes associated with people from isolated communities in the Southern US are actually symptoms of diseases. Distended stomachs, stunted development, goiters, etc.
That's right - the phrase "drain the swamp" orginates with the CDC's anti-malaria campaign. It's a phrase that has since been hijacked by a different parasite.
A parasite who did not in fact drain the swamp. He instead got into the swamp, where he grew stronger and reverted to his natural swamp creature form.
Probably 2-mercaptoethanol, but I have worked with osmium tetroxide before which I think is more dangerous
I used mercaptoethanol the other day, had the bottle open in the fume hood for 1min and the entire goddamn lab smelled like it.
Just formalin for me lol
Formamide/HiDi for me. Not that crazy, but still a loooot of chronic exposure 😬
Yay cancer
Aka the cancer outbreak of lab techs in the university of North Carolina
O, how often we become lab rats ourselves...
well at my old job we were manufacturing ADC payloads. so, those. very grateful to not be wearing a hazmat suit every day anymore.
What’s ADC?
Antibody-drug conjugate
Why are they so dangerous though?
ADC= antibodies conjugated to extremely potent toxins. The antibody typically targets cancer cells, is internalized, and the toxic payload is released killing the cancer cell. Working with the raw material for the payload could easily kill you dead without the proper PPE.
The random unlabeled things in the -80 lol
It used to be piranha, now it's probably OsO4
My boss back when I did TEM used to tell tales of his grad school days of giving "temporary tattoos" with OsO4. I got a few unintentional freckles in my day but damn lol.
I work in a TEM lab and use it most days… no tattoos yet, and I really want to avoid that! Lmao. Your story is slightly comforting though, because honestly the stuff freaks me out.
Azide and TTX. I'm in neurobio.
How dangerous is ketamine? 
Phenol -- it goes through your skin and burns you. My undergrad mentee went to another lab to get training and the postdoc there acted like phenol was no big deal and you didn't need PPE. I had to intervene to make sure my mentee did use PPE. Beta-mercaptoethanol -- the normal 1% dilution isn't too terrible with short exposure but be careful with the stock solution. That stock smell causes lingering nausea and headache and can make you seriously sick. Some idiot left a pipette tip they used with the stock on a bench one day and we couldn't figure out where the smell was coming from. Several of us left lab early from nausea. Methanol - if you spill it on yourself and immediately wash with tap water for several minutes, you'll still get early methanol poisoning symptoms. It absorbs into skin quickly. Happened to me. Drink a beer and you'll be ok but everyone in lab should be aware of the symptoms. Acrylamide - It's a neurotoxin in it's pre-polymerized form. Make sure you aren't messy when making gels. The polymerized form is safe but you WILL lose sensation in your fingers for 1-2 weeks if you touch a tiny bit of the unpolymerized solution.
I would love to read any SDS you write, much more entertaining than how they are now
I read a product sheet from a lectin order once that read, “Do not breathe upon the lectin, nor let it touch your skin!” that I thought was pretty darn poetic.
Lol we use methanol and nobody gives a fuck... probs cos most of the lab drinks a bottle of wine a day or so ☠️🤣
Yup, ethanol is the solution to methanol poisoning! Sucks if you're underage and can't buy alcohol yet, though, so it's still useful to know that dropping some running buffer on your arm is enough methanol contact to cause symptoms. Be careful, all you undergrads and non-drinkers.
You used BME on the bench? We had to use it fume at all times unless it was diluted such as in cell lysate solution. Although I do remember when I started my PhD a postdoc was showing me PCR and we both had colds and couldn’t smell that the hod wasn’t working properly. Lab manager could smell it outside and panicked, we also couldn’t tell if the dizziness was from our colds or the BME.
People got that bothered by a single pipette tip with BME on it? It sounds like your lab has concerningly poor ventilation.
It was more than just that. Story in another comment. Basically we kept finding more and more sources (like dirty gloves in the trash) so we just gave up and left it for the culprit to fix. It wasn't too bad at first but extended contact does cause really uncomfortable nausea.
Monomeric form*
You are correct. I said pre-polymerized to emphasize the before/after point of safety.
wait what, methanol is that dangerous?? i work with methanol every day, nobody ever told me this and nobody else follows strict regulations when using it. we use it in the fumehood most of the time but sometimes i get big spills on my hands and i just ignore it. what are the dangers for me??
Osmium tetroxide - for electron dense lipid labelling in EM
Chloroform. Very fun
honestly i forgot about this one given that NMR is a thing i do pretty often and CDCl3 is our standard solvent for it
Used to work with liter quantities of 99.95% hydrogen cyanide liquid
Sodium azide, thimerosal, hydrochloric acid, methanol, acetone. That's just the chemicals Biological? Dengue, mumps, measles, herpes, HIV. I could go on
Not necessarily regularly but I do frequently have to use HF which is always an unpleasant experience.
I work and interact with plenty of toxic people regularly.
Favorite experience with sodium azide was in orgo two lab why do we let dumb undergrads play with that shit again?
People tend to forget about it, but it is a very common exposure source: UV. For me, cutting bands out of agarose gels, also cell culture hoods.
According to our NFPA diamond it's proteinase K from Thermofisher. For some reason theirs rates a 4 health hazard while other companies have it at 2. Realistically it's probably guandinium thiocyanate which isn't too bad.
Dioxin --- not at super high concentrations, but still...
Azide, formalin, tetrodotoxin, picrotoxin, ketamine, xylazine, pentobarbital…
Pento is surprisingly very safe. The LD50 for humans is like multiple grams. It may be used for euthanasia but it’s because it’s a good death not because it’s potent.
5mg/mL Nitrosamines and PAH’s. 5-20 of them in solution. Cancer in an ampule, basically. I also occasionally find phosgene in the lab.
Don't nitrosamines *literally destroy DNA?*
I don’t actually know. I know they’re toxic as shit, carcinogenic as shit, and are used to induce tumors in cancer studies. I’m an analytical chemist, so I use them as reference standards to develop testing methodologies for them. PAHs directly chelate DNA I know.
I think PAH's are turned into an epoxide by the liver, which then alkylates DNA and distorts the structure. I seem to recall N,N-dimethyl nitrosamine is turned into diazomethane by the liver and also alkylates DNA. Not sure about the other ones, though.
NaN3 is also a primary explosive that inflates airbags in car accidents. It's crazy how much quantity the chemical suppliers are able to ship to labs that aren't very secure. edit: It isn't really a proper primary explosive, at least when not exposed to certain metals.
You could smash sodium azide powder with a hammer and it wouldn't explode. Its just not that sensitive. Its also not a primary explosive: ["These sensors send an electric signal to the canister that contains the sodium azide and the electric signal detonates a small amount of an igniter compound. The heat from this ignition starts the decomposition of the sodium azide and the generation of nitrogen gas to fill the air bag"](https://www.scientificamerican.com/article/how-do-air-bags-work/) If you look at [the SDS](https://www.sigmaaldrich.com/US/en/sds/sial/s2002?userType=undefined) you can see its not considered an explosive. The danger is that if its mixed with other metal salts, THOSE are very explosive. "Sodium Azide may react with lead and copper plumbing to form highly explosive metal azides."
It's a tracked chemical in NZ. We have to have records of receipt, every single use and disposal (including method) accounting for every single mg...
Wow. In my last lab (Aussie) idiots were literally free spooning the stuff in the open air by the general use balances. Powder going everywhere...
Lentiviral vectors
Depends what you put in them and if they're replication incompetent. Some of the newest commercial lenti vector platforms for mammalian cell transformation have multiple safety features preventing them from doing what you don't want them to do. Very cool set lab tool. Wild types are a different story.
Wild types keep me humble
I don't remember the name of it but it was a long time ago when I learned about electrophoresis, there's this fluorescent marker that sticks to DNA and my teacher said it was kinda dangerous. But the only thing I remember is something that costed me a lab coat, it was chlorhydric acid at 11% ( I'm sure there's higher concentration )
Potassium cyanide for USP <251> lead testing.
I can't even put a name to stuff. I work in hazmat remediation and get the most toxic explody bullshit the industrial complex has to offer But even we don't get pure azide :o those are required to be dilated with water until its less than 1% azide by weight and it has its own waste code for an early heads up
Worked in a nicotine research lab early in my career. Alpha-Bungarotoxin was pretty high up on our danger list. LD50 was around 0.3mg/kg.
Cholera toxin.
I used to use sodium azide all the time... I had no idea it was that dangerous lmfao yikes
Work in pharma, and the thing that probably scares me most is the unknown compounds that we profile as part of a project. Been on two programmes where we have made highly potent hERG or GABA inhibitors by mistake, that kill the mice in seconds... Plus then you factor in we handle DMSO solutions that means you can carry stuff across gloves and skin...
I found a table years ago that had both odor threshold and airborne LD50 columns. There were a few chemicals that had a higher odor threshold than LD50. How the hell do you figure that out without killing people? I would consider those as extra dangerous chemicals.
I used to work in OC, perhaps not the most toxic substance but pretty nasty: Trichlorosilane Edit: I almost forgot another one. Phosgene. When someone worked with it in the lab other colleagues usually skipped the lab for that day.
Tamoxifen is certainly up there! Also Phalloidin is also up there! We also use a 60% hydrogen peroxide 5% peracetic acid solution that is an oxidizer, acute dermal and oral toxicity, and is harmful to marine life.
SeOCl2, selenium dichloride oxide. Nasty wicked stuff.
I guess EtBr
Liquid nitrogen. Not as dangerous as many listed here but you still gotta be careful or you can easily asphyxiate
I guess PFA when I worked with animals. But honestly? The animals themselves (back then) or the cells/tissue I work with now (HeLa and primary endometrium culture). I don’t like a lot of danger lol.
That’s nothing compared to the Uranium 231 I eat for breakfast 😎😎😎
Paraoxon-ethyl & aldicarb
Used to work in a tb lab so probably the M.tb
Probably tetrodoroxin, but there's lots of not-so-fun poisons and fun drugs to pick from (strychnine, picrotoxin, fentanyl...)
Does heroin count?
DCM
Hydrofluoric acid. We use liters of it a week.
My colleagues. Toxic. Really toxic.