Good morning everyone. This is the 11 o'clock session on Leveraging Existing Guidance to Enhance Occupational Health Response to Biological Exposures. I am Paul Meacham, this is Marianne Sondrini, as you can tell we have got a lot of space and if not an overwhelming audience. So maybe, you know, I understand that people like to sit in the back of the bus and kind of, could you move up so we can have more of a conversation than a lecture. And Marianne is going to talk about it in just a second. We really wanted this to be more of a dialogue than a monologue. And so if you are in the back, there is going to be a problem. So please feel free to move up. We don't bite often, hard. We have broken the skin lately. Turn this over to Marianne to start. Hello everyone, I am Marianne Sondrini and I am the director of the Eagleson Institute in Maine. We are a non-profit foundation with a mission to educate the life science communities on the principles and practices of health and safety to protect workers. And I have had a relationship with ACOM now for about 15 years because ACOM has been a co-sponsor of our colloquium which is Preventing and Treating Biological Exposures coming up in June in Virginia. It's designed to bridge the gap between occupational health and biosafety. And that's what we hope to do today with today's presentation where Dr. Paul Meacham is going to be talking about handling exposures based on guidance from biosafety. So it's a little different than other presentations here. Paul is a biosafety consultant, but he began his career in biosafety after a career in research at Merck where he was corporate biosafety officer. And then he went on to CDC where he was the senior advisor for lab safety. And in that role he was editor of the latest version of the BMBL which he'll tell you about. Previous to that he was at CDC director of environment safety and health compliance where he had a staff of 87 people and they were responsible for the safety of employees, of contractors and visitors to CDC as well as protecting the environment there. And he could I know I worked with Paul for many so many years I know he could speak weeks on this topic weeks and he'd like to address what you want to hear. And so we have he has a presentation but he can expand different areas or address topics not included based on what you'd like to hear him to discuss today from his perspective. So we'd like to begin. Could you just tell us what you hope to get out of the session. A few people could tell us it would really help direct it in a way that you'll benefit. And here comes Warner. Unfortunately the only mic is over there. Oh there's only one working mic. OK. So I want to make sure that we don't have both microphones live because that would be very bad for you and for me. OK. So we've got some ideas what to talk about. I've got a bit of a scaffold for a talk. We're going to ignore a lot of the scaffold to be able to answer your questions and talk about that. Just want to note that we don't have any conflicts. Marianne is the executive director of the Eagleson Institute does a number of conferences that are done in conjunction with a com. So if I do mention her occupational health colloquium this summer it's not inherently a conflict of interest. I said I did work for Merck for nearly 20 years. I'm not going to try to sell you any vaccines. It's not my interest. The nearly 10 years in the CDC. We don't sell you anything either. And when during COVID not everybody would buy what we're selling anyways. I am the past a past president of the American Biological Safety Association or ABSA. I may mention them along with a whole with some other ancillary trainings or things like that. I'm also not trying to sell you any of that either. It's basically informational. So we're trying not to try and minimize the conflict of interest. So in designing this talk first thing that came to my mind is how do we define the relationship between you and the occupational health community and those of us on the safety and specifically the biosafety side. Is there a term of use that you would describe your interaction with them or your association with them. So this is now answer. This is now the audience participation section again. How do you describe your your association or interaction with them. Is it ineffectual. Is it. Who are they. Is it. We know who they are. We wish they knew who we are. I'm hoping none of those are the answers. I'm hoping that there is a professional relationship and I'm hoping actually the answer is that you see them as partners. Now I was incredibly fortunate at Merck. I had two professionals Dr. Peter Nigro and Dr. Yvonne Sir. They partnered with me. And when we came to difficult decisions like the question regarding the use of well you didn't actually ask it during but before we're discussing vaccinia and pre-vaccination and whether risk versus benefit. Now at the time the only vaccine that was available was a camp 2000. We had to make a decision as to whether or not we would then vaccinate our staff who were handling vaccinate as a vector with the a camp 2000 to deliberately infect them with the very agent for which we were trying to protect them. And then we'd have to protect the people who are giving the vaccine i.e. our physicians our health physicians some of whom had underlying health concerns that disqualified them from giving the vaccine. So what would the relationship between be between them and the people giving the vaccine are they now at risk. In the end our risk assessment for us by us was we were not going to vaccinate people that the risk of a person being inappropriately exposed was relatively low because our controls were good but the risk of a secondary effect from the vaccination the deliberate exposure to the vaccine outweighed that and that's where partnership works. I wasn't actually in favor of that I actually wanted them vaccinated because to me a failure by having somebody have a vaccination have a postulate on their hand or worse their eye was bad was terribly bad and that the idea that it would be on their arm they could control it would be fine. But through a discussion with my partners in occupational health the decision was reached as a corporation we wouldn't do it. We're hoping that if you don't have that relationship with your people that you have that discussion you have that literal come to Jesus meeting because you need it they have information you need and you have expertise that they don't. They will never be occupational health professionals. They may be very skilled in what they do but they're not skilled in what you do. So things have come up lately. Mary Ann was kind enough to note that there is a new edition of biosafety and biomedical and microbiological laboratories BMBL 6th edition. If you have one of these beautiful books in red it's a paperweight it's a collector's item I know. But the 6th edition is out came out in late 2000. You can get a copy online you can order a hard copy online if you are like me where you have a computer screen with a page on it because you can download it. It's nice but it's not paper. And so you can order a hard copy from CDC info online at U.S. Post Office is only OK so I'm sorry if you're an international colleague if you're an international colleague have it sent to an American colleague and have them ship it to you. But it's not an overwhelming change in the document from the 5th edition to the 6th. So if you have had a copy of the 5th edition and you haven't been able to get a copy of the 6th yet don't sweat. The changes were relatively modest. There were some significant ones but it's relatively modest. There's another book that came out roughly the same time. From the World Health Organization WHO has an international biosafety guidance document the Laboratory Biosafety Manual or LBM. The 4th edition of it came out in December 2000 sorry 2020. At the height of COVID virtually nobody's heard of it. Talk about it in a second. There are some significant things you should know about it that differentiate it from the U.S. guidance. So for those people that are here that are like OK you know I'm somewhat comfortable with biosafety. I know it exists. We've got it in our facility. Our clinical labs are all BSL 2 but beyond that there are some things to keep in mind. In the BMBL we describe the 4 control levels, biosafety levels. Canadians call them containment levels. UK does the same thing. EU does. There's 4. From biosafety level 1 which is basically a laboratory you can do open handling to biosafety level 4 where you're in a chemical suit and everything's handled inside a biosafety cabinet inside an air pressure tight room. So for most of you you're going to be seeing work at biosafety level 1 and 2. Biosafety level 2 is for run-of-the-mill pathogens, Salmonella, E. coli, Shigella, mumps virus, things like that. 3 is for something SARS-CoV-2 where you're worried about an aerosol transmission. So you can use that information. If you don't have a pipeline from your occ health people to your safety people and somebody comes to you after an exposure and the first question out of your mouth is what containment level were you at? What biosafety level were you working at? It will give you information as to the controls that should have been in place. So they say, oh yeah, I was working on SARS-CoV-2. You automatically go, hmm, you're working at biosafety level 3. Everything was supposed to be working in a primary containment vessel like a biosafety cabinet. And they say, oh yeah, we were working on the open benchtop. You have information regarding the ability of that laboratory to do its work safely and your risk assessment should automatically be adjusted to higher levels of risk because they're not using the controls appropriately. Now one thing to keep in mind. In the U.S., this is guidance. There is no federal law or regulation that says thou shalt follow this. It did not come down in stone tablets. It's 600 pages. That's a lot of tablets. But this is best practices. So you don't go in here and say, oh, well, on page 42 it says you do this. The question is, it says on page 42 you do this. What did you do? Are you wearing gloves? Well, no. Well, why not? And if there's a reason, well, we're doing it using a robot. Okay. Good reason not to necessarily be wearing gloves. You're on the outside of the robot. As long as it meets the ANSI standard for robot safety and it was being appropriately ventilated, you may not need gloves. Okay. But there needs to be an understanding as to what their practices were that deviate from this. It's not if they don't do it, it's illegal. But it could be a problem. Now there are other groups in the United States who treat it like a regulation. I have nothing to say about that. But those of us that put it together, that edited it, made it clear, it was not generated as a regulation. One other quick point, because it's going to come up in the next slide that's going to be important. The BMBL strictly adheres to the hierarchy of controls. If you have the opportunity to have an engineering control, a biosafety cabinet in place, you ought to have one. So when you're talking to somebody who's working with SARS-CoV-2 and they're working on manipulating it, growing it, amplifying it, and they're doing it in the open, you've got a question that you should be asking. Because they shouldn't be doing it. That's how we go after it. The issue is, oh, okay, some other things. The issue is the international one is different. The quick things that have changed a little bit in this. For you in the occupational health program, we don't recommend serum storage anymore. Banking. It was a disaster. How do you maintain chain of custody? How do you maintain the storage conditions? How do you decide to deaccession it? How do you get the approval from the person that you got the blood from 30 years later to be able to throw it out? It's a mess. So our recommendation is, in the event of there's an exposure, that you take a time zero blood sample for baseline. Don't serum bank. It's just... It's a risk assessment, and if you've got something, you're working with a chronic disease, you may choose to serum bank. If somebody's working with HCV, you might choose to, or you might choose to take a sample at their employment physical and test it for HCV and store the result. A lot better than storing a blood sample for 20 years and then trying to analyze it. But that's a risk assessment. That's an assessment that you as a health professional make. We're not recommending a health review for anybody working with animals at all containment levels. There are significant risks, as you well know, for handling animals in vivaria, especially where housekeeping practices are not particularly rigorous, where they're doing dry sweeping, or they have cages that aren't HEPA filtered, or they're not using micro isolators. And so the dander level is significant in those facilities. Losing a 30-year staff every five years, which had been the previous average, it was shown by ALAC about 10 years ago, that's unacceptable. And as occ health professionals, and safety professionals, we need to be doing primary prevention, making sure that we're making these people aren't developing allergies that kick them out of their chosen field. There is a section on occupational health. However, if you're here, my expectation is you are an expert in occupational health. And so this section is really designed for those people who don't have it, and it talks to the research community and the safety community about what you do for them, more than it talks to you about what you do for the community. But it might be something you want to advertise to your staff that, oh, by the way, this is how we work for you, and how we partner with you. If you've got international partners, you've got a problem. This is now the international set of guidance for laboratories handling biological agents. And it is a complete overhaul of their guidance. They said the Americans, the Canadians, the Europeans, have four biosafety levels, biosafety one through four. Lowest is one, highest is four. Internationally now, there's only three. There's a core lab, which is equivalent to a biosafety level two lab without a biosafety cabinet. You can handle things in the open as long as you're careful. There's maximum containment, which is equivalent to biosafety level four. You're in a full chemical suit, air supply, sealed facility, working with the worst possible viruses on the planet. Everything else is what's called core plus. So there's no longer a mapping. If you're in the United States, and you have a risk assessment, and you have an occupational health program for your American colleagues, and then it's being ported to an international location, it may no longer work. Because now, they're more emphasizing, instead of the hierarchy of controls and the engineering controls, they have expressly said, we don't follow it. to them, administrative controls, including the competency evaluation of staff, can be substituted. Now, does that make sense? And the answer is, actually, it kind of does. If you're in a resource-limited country and you've got to buy a safety cabinet and you can't afford to have somebody come and certify it annually, do you really have an engineering control? No. Does that change your risk assessment? Yeah. Does that change the level of risk that person is assuming? Sure. And you, as the occupational health physician, do you need to, or occupational health professional, do you need to take that into account in determining the likelihood of an exposure and whether or not we need to change any of our occ health surveillance or prophylaxis, pre-exposure prophylaxis, for those individuals that are working under those conditions? The answer might be yes, but it's a change to the risk assessment that we have to take into account. We can no longer simply map what's done here or other industrialized countries to the rest of the world in terms of their safety performance in handling biological agents. Okay. So, what do we do? What is it from my side, the biosafety side? What do we do? This is it. 90% of what we do is risk assessment. That's our job. We're the boots on the ground people going to the laboratories, going into the clinical areas, and assessing the risk of the work that's being done. It should be standard, right? Everybody should be doing it. But in the United States, it's only required, if you're working with recombinant materials. Because the BMBL, which does talk about risk assessment in a full section, is guidance. The U.S. National Institutes of Health, NIH guidelines for recombinant synthetic nucleic acids, is a condition of the grant, right? You get money from NIH to do recombinant research, you must comply with it. And they require a risk assessment. Nobody else does. You may want, for your needs, partner with the safety people to ensure that everybody does. Because at the end, I've got a scenario, it's true, where we didn't, and we paid for it. There's an entire section on it. So if you have never seen the NIH guidelines, and I'm probably speaking to the choir, we all have them. You can download them from there. There are no hard copies, it's all downloadable. I was gonna say print them out, but it's 100 something pages. Print them out at work. I'm now a consultant. Every copy I print is coming out of my pocket. There's an entire section on doing the risk assessments in section 2A. Take a look at that. I hope everyone here has seen this. If this isn't boring and redundant, oh, we need to talk. You may see it slightly different. You may see it as PDCA, Plan, Do, Check, Act. That's fine. The number of steps may be slightly different. Some have four, some have five, some have six. It's not relevant. The key things to the risk assessment is to identify the hazard. Okay, first hazard. And by the way, a hazard is simply the intrinsic property of the molecule to cause harm or the agent to cause harm. Ebola is a hazard. Ebola down at the CDC in the freezer at the BSL-4 lab is the risk. We're not at risk. Right? Okay, so the difference between the two. We identify the hazard, and then we look at the risk. Well, the risk, since it's down in Atlanta in a freezer in a BSL-4, eh, we're pretty good. But somebody who's getting a sample from somewhere and they're non-human primates is asking the question, what's the risk? Okay, so let's discuss it on B virus. Highest risk material, neurological tissue, brain, CNS. Next time, it's the kidney. We have never been able to culture B virus from blood, ever. Does that mean the risk is zero? No, it means we haven't found it yet, right? It's a black swan conundrum. Would I worry about tissue that came from a non-human, a macaque, a rhesus macaque, because only they can contain B virus? And everybody knows about B virus, right? I'm not throwing out a term. Everybody goes, is that like hepatitis B? Which we'll talk about later, because in one case, head colleague went to their emergency room after an exposure with a non-human primate, with a macaque, took that information to the emergency room, and the physician went and lectured them on, oh, you've had your hepatitis B vaccine, I don't understand the problem. Yeah. But you want to identify the risk. What's the risk in getting a lysate from a non-human primate source at another institution? Is it zero? No, it's not zero. They heat treat it. Okay, so what questions do you ask? Is the material solid or liquid? Was the material at 56 for 30 minutes, or was it put in a 56 degree water bath for 30 minutes? And originally, it was at minus 80. Slight difference in terms of the actual time at temperature for inactivation. Yeah. Did it change the risk? Yeah. Is it a question that your PIs should ask? Yeah. Do they? No, no. No. No. But those are the sorts of, that's going back to evaluating the risk. Now you go back to the controls. Somebody's handling non-human primate material, am I going to still assume that there's a residual risk? I am. I am, especially because they're handling a liquid. And we all know researchers always wear their safety glasses. Nobody busts out laughing. I do, every time I hear somebody say that sort of stupidity. You're barely wearing lab coats, hit button, please. If they're not handling it in a biosafety cabinet, and they're not handling it with any sort of eye or face protection, do they have an increased risk? Yeah, they do. So I would be recommending that they not be handling that on the open bench top, even though it's been inactivated. Have they validated the inactivation process? No. We read about it somewhere, that 56 should do the job on BVARs, and it should. It should, absolutely. But if you didn't validate it, under your conditions at your institution, it's not validated. And they didn't verify it, because they've never taken a sample and tested it. So they failed the validation test, they failed the verification test. No. And so your assumptions are correct. I would be treating it as though it's a possible risk. Is it lower than it would be if it was native material? Yes. Oh, and by the way, if they tell you it came from a B virus-free colony, you know what the correct response is? Laughter, yes. No such thing. Okay, no such thing. Because even though you test an animal at a given time in its life, at other times, and it will come back, the sample will come back negative, under the right conditions of stress, they will, almost every animal that is no longer an adolescent, every adult animal, will test positive at some point. Best guess is it's an STD, an STI. That's the one I'm trying to, oh, yeah. Nope, keep him away from that. Keep him away from that discussion as well. So now we're back to determining the controls, and we did for the B virus. Recommended no open handling. Did it be back in the biosafety cabinet? Check to make sure they actually implement the controls. That's not a knock health problem, that's a me problem. That's the safety people's problem. And the PIs, they own that. They have to check the effectiveness. Have they changed anything? Well, you know, we thought we liked getting the lysate so much, we're getting tissues. Did it change, change the risk? Yeah, yeah, absolutely changed the risk. So when you get a risk assessment, how long is it good for? Should you be reviewing them? Should they be reviewing them? Yeah, and again, this goes back to the partnership that your safety people should be going and asking, at least on an annual basis, everything's still okay? Everything, nothing's changed? Because what happens is mission creep. We liked getting the lysate so much, we're getting tissues now. And that changes the risk. Because now I've got to make sure I've got that heat treatment all the way through the tissue. It's easier with liquids. Solid tissue's gonna be much more difficult. Oh, we got new staff. Great, have they been trained? Ish. Changes the risk assessment. We got a new piece of equipment. It's open on the bench. It's a little, it's only a little tiny robot. Great. Generate aerosols? Well, the pipettes do blow out. That's the definition of an aerosol. So you want this process to be iterative. It's not necessarily, this isn't yours. This is the safety people's. This is the PI's, this is the researchers. But you should be involved in this. This information should flow through your office. Not necessarily everything that you make the decision on, but when there are changes that affect your occupational health decisions, this needs to come to you. Oh, I hope, oh. I can't do this, can I? Is it possible, Steve, to be able to open that link? Because what I really wanted to do is show you one. Oh, perfect, thank you. Unfortunately, I can't, okay. So whether or not you're engaged in the process or not, you should be getting, you should have access to these. So you can go to the website, you can go to the website, you can go to the website, you can go to the website, you can go to the website, you can go to the website, you can go to the website, you can go to the website, you can go to the website, you can go to the website, you can go to the website, you can go to the website, because this is how each individual group at an institution should report its risk to you. And you should be able to see this. Gives you the easy stuff, right? Who's in charge? Where is it being done? Animals? Could we go to the next page? Please, keep going down. My apologies for making you do this, but it's the important stuff. So here, they're actually giving you the hazard. They called it the risk. Is it? What do I know about that? Nothing. Nothing. I now know the agent by genus and species. Great. So I got Bacillus anthracis. Useless. But it did help in one sense. I now know the basic level of concern, right? Because they told me it was, no, it could be E. coli, which could be biosafety level one or two, depends on what happened. Or Bacillus anthracis, could be two or three, depending on what you're doing. But it gave me some area that I can start to determine the risk. Here, I'm getting a little bit more of the risk. What are they doing? Is there a problem with it, though? In your trying to figure out what sort of medical surveillance they need, or post-exposure assistance they might need, is what they're telling you going to be enough? Not even close. They didn't tell me how. They didn't tell me how much. Right? I could be using, I don't know, E. coli. The K12? Or O157H7? I don't know. They didn't tell me. Am I using a milliliter of it? Am I doing a hundred liter fermentation of it? I don't know. So I get some information, but not enough to go through it. Can I go down to the next page, please? Oh. I've got some considerations. Oh, this is good. Do I have a biosafety cabinet? Do I have autoclave? Do I have PPE? I'm actually looking at mitigation. Problem is, I still don't know what you're doing. Right? Do I know if they need a biosafety cabinet? I was doing cloning with E. coli K12 strains. Do I need a biosafety cabinet? Nope, I got one. Oh, that's nice. I've got PPE. Is that necessary? Oh, we're in N95 respirators. Does that trigger anything for you? Well, yeah. Respiratory protection program. They have to be medically cleared before they're wearing one. Nice that you got that information, right? Keep scrolling down. The guidelines aren't really useful, please. Keep going one more page. There we go. So I want to know some interesting things. Deliberate drug-resistant trait? You'd want to know that, wouldn't you? Or antibiotic markers? Are you increasing the pathogenicity of the pathogen? Would those be things that an occ health professional would want to know? I would. Are you working with vaccine? Are you working with ectomelia and you're adding IL-4? Putting it back in mice? Hmm, anybody ever do the experiment? Australians did about, what, 15 years ago. What happened? Killed all the mice that were vaccinated. All of them. Hmm, didn't think it was going to be a big problem. They didn't either. They were wrong. But it changed the pathogenicity. Does that have ramifications for human health, for occupational health? If they then decided, maybe we do that with vaccinia. Even if it was MVA, I'd be concerned. Does this meet your needs? I can tell you that as much as I like these guys, and this is actually a very good university, I thought this didn't work. It didn't lay out what the hazard, it laid out the hazard, didn't lay out the risks. It actually asked if I was working with a centrifuge, but didn't say I was working with a sealed rotor or safety cups. So it didn't tell me that, it didn't tell me exactly what the risks were, and it didn't tell me how they were mitigating the risks that they did have. But it gave me some hints of things I want to look for. Are there going to be issues about post-exposure prophylaxis? Maybe. Did it give me an idea that this could be increasing the hazard caused by, the risk caused by the organism? Absolutely. So as the occupational health group, if you got to see this, would this be an opportunity for you to go back to the Institutional Biosafety Committee and go, ladies and gentlemen, this is very nice, thank you very much, but it doesn't meet our needs. And honestly, it doesn't meet your needs either. Because it doesn't. And so this is where the partnership comes in. What happens with these committees? Becomes groupthink, right? And don't get me wrong, I've been on the leading edge of this sort of stuff, and I bring these things in, everybody looks at them and goes, well, okay, looks good to me. But you come at it from a different perspective. And so having your voice present, and having you come back and push back when it's not meeting your needs, is not just good, it's essential. Because otherwise we miss this sort of stuff. And when we miss it and something goes wrong, it falls on you to fix it. Right? Somebody comes to me and says, I accidentally splashed myself with salmonella in my eye. That's no longer a me problem. That's a you problem. It's a me problem afterwards going, how could you have let somebody do that? And I'd say, well, they should have been wearing goggles. They did, they had them on the top of their head. But it becomes an occupational health problem to deal with the after effect. Okay. Can we go back to the slides? Thanks. And as you can tell, I hate being in front of a podium. Okay, perfect. Ooh, I think we may have gone a little too fast. Okay. So if you're not, and I'm hoping all of you are members of your organization's IBC, if you're not, force yourself on it. Be polite, but be firm. You deserve a seat at the table, and they may turn around and say, oh, but according to the guidelines, it's only five people. No, it's not. It's a minimum of five. Okay? And it may have a different name because an institutional bias committee is only the recombinant, and only if you get NIH money. You have to have one, and so a committee that sees everything may have a different name. It's okay. You don't care about the name. You care about the function, and so if they do recombinant, non-recombinant, they may give it a different name. Okay. But be on the lookout for it if you're not a member of it. Also, the big thing, it may not give you automatic access to the assessments. They may do it like an IACUC does where they have two primary reviewers. You want to see it all. You may not review it all. That's okay, but you want to see it all. They also may be paper. Oh, I hate paper. I understand paper. I do, or PDFs. They're easy to make. I put them up. It's all nice. But then what happens to paper? It gets filed. Right? How do you mine paper? How many people are working with non-human primate, macaque tissue in your institution? Do you know? Well, it's in the files. Mm-hmm. And if something went wrong and you found that somebody was working on an open benchtop, could you go and you identify everybody who's working with it so you could go back and say, or have the safety office say, you need to be handling that inside a biosafety cabinet, or you shouldn't be handling that in the open. And so here's the second opportunity. That if you are on the IBC, and they do have it only on paper, maybe this is time to consider an electronic system. I'm not dropping names, although apparently Cordy is here as a co-sponsor of the, of this event. The nice thing about being able to mine that data is when something goes wrong, you can figure out what's actually happening. Or you can get ahead of it. So everybody knows about the Blood, Bone, Past and Standard, right? Everybody knows about it. Oh, my God. I'm tired of hearing that from 1991. That's not enough. Do you know, at your institution, whether everyone has received the vaccination or signed off on a declination? Everyone who is under the authority of that standard? Everyone? Because what frequently happens is people come into a laboratory, right, and they register with the safety people because they have to take the training. And in the part of training, it says, check this box if you're doing blood-borne pathogen, or take the blood-borne pathogen training online, which is actually technically not allowed. But we won't talk about that today. So they have a database of everybody who's taken it. Can you match their database against yours, showing that they have either given you their titers, or been vaccinated, or signed the declination? Those are your three choices. So there's an opportunity for you to mine their data to make sure yours is working well. And you can do it for anything. All of it. But it's not easy to do if it's paper. Unless you've got some really dedicated students or admins who are willing to go through all of the paperwork. And I've never seen that happen. So every once in a while, people have had some occ health professionals, really good ones, have come in and said, you know, I was in, and they were talking about a third-generation lentiviral vector that had an mCherry insert. And then it was being driven off of a tet promoter. What the hell is mCherry? Is that like something that goes on a Sunday? Third-generation? Okay. It can be overwhelming. You are medical professionals. Wonderful. And that's a field of study that takes years to hone. But your knowledge of lentiviral vector systems may not be all that great. That's okay. It's not your job. It may not be your job. And to know what the mCherry is, which turns out to be a red fluorescent protein, you don't necessarily have to know that either. But they show up in these IBC registrations. Or if you're doing human geotherapy. And the vector systems combinations are overwhelming. Okay. And you turn around and think, well, you know, I'm the occ health physician, and I should really know this stuff. But I don't want to look like I'm stupid. First of all, you shouldn't. There's no embarrassment. You're a medical professional. At any, whatever your medical degree or whatever your medical skills are. You have a skill set. This doesn't have to be yours. But you can dip your toes in it from an easier position. Every institution in this country that receives a dollar of recombinant money from NIH has to have all of the recombinant work approved by the IBC. Two of those people have to be community members. They can have no affiliation with their institution. Do you have any idea how easy that is to find somebody who wants to be able to get in, to look at that and have no connection to your institution? They'll kill to have you. And it's an easy way in to both be an affirmative member of the community and to learn what other groups are doing. And you can do it at a lower college. You can do it at, say, a community college. Or one of the smaller state schools in your area. So, I'm in Baltimore. So, and forgive me if anybody's from Townsend. So, instead of going to the University of Maryland or going and doing it at Johns Hopkins, you say, I'll volunteer with the Townsend IBC. Okay. Mid-level university. They have recombinant research. But they're not going to be a Hopkins. They get help. You get information. And as the outside member, you can always go, I don't quite get why that's third generation and not second generation. And get them to explain things to you. That forces them to be better and gives you information that you could use to take back to your institution. Even if you're at your own institution, invite yourself to a lab inspection. I have never had a safety office say no to one of their occupational health people tagging along into a facility visit. Never. And it can be eye-opening. You go in and A, you can be appalled. Or B, you can be impressed. And sometimes both in the same day. But it gets you into the place. Allows you to tag along with somebody who should know the facility intimately. And help you integrate what you see at the institutional level with what they see at the very granular level. You can get courses. If you're not a molecular virologist. And God knows why should you be. But if you're doing work and it's coming in that you're working with your institution's working with second generation lentivectors. Or third generation lentivectors. APSA has courses on it. AIHA has courses on it. You could go to the occupational health colloquium where there was a significant discussion. Was it two years ago? On administration of prophylactic antivirals after lentiviral exposures. I think longer than that. You publish, you did a published paper on that. Actually there's going to be an update. Oh, there's going to be an update on it. Now, actually, personally, as a safety person, I didn't agree with the results. To me, I don't care what generation lentivector it is. You have a probability, a finite probability, it's non-zero. A random integration of the human genome. So if there's an exposure of a lentiviral vector to a human, to one of my staff, I am going to recommend to my occupational health people that you treat them with antiretrovirals. It's a weak therapy. It's not particularly difficult in terms of the side effects. And if you're wrong, you have a problem on your hands. Now, mind you, if it was a, back to the mCherry. If it was simply a fluorescent protein, green fluorescent protein, yellow, whatever. Is it a significant risk? No. But if it's an ocular exposure and they're exposed to far blue light, their eyes may glow green, which they may love at Halloween. But in terms of actual effect in the metabolism of the cells, it's not likely to be a problem. And so you could stratify. And there are groups that have argued, including the group of the colloquium. They said if it's a low risk insert, don't treat. That's a risk assessment that you as the medical professionals make. Me as the safety professional has a different opinion. And that's where we collaborate. And in the end, medical people won that argument. And we have had situations where there have been low, there have been exposures to low risk lentiviral vectors that had no sequences of homology within the genome that was being exposed, i.e. human. They weren't oncogenic. They weren't immunosuppressive. And therefore, the risk was deemed to be tolerable. Okay. But that's a discussion that you should have before somebody gets exposed. Because if you let that discussion go until afterwards, how long does it take for you to come to a resolution at an institutional level? Have you done it yet? Exactly. So, okay, what? Okay. So, I want to close with a case study. Because this is where things have gone wrong. And this is where we need you. Where we collaborate. And it also points out where that risk assessment process, it can fail. So, that applied environmental microbiology is actually a reference that helps understand all of this. Lab was working with significant pathogens, public health pathogens. And they decided they were going to do a digestion. Basically, a protein digestion of these organisms. And then run them on a mass spectrometer to see if you get essentially a fingerprint, a molecular fingerprint that would give you a rapid diagnosis of that agent. So, they did it using Bacillus anthracis. Bacillus anthracis aims. Okay. Harvested a colony from a plate, 24-hour plate. Digested it. And a buffer recommended by the manufacturer to do proteolysis. They took an aliquot and incubated it for 24 hours. Make sure there were no colonies. There weren't. Nope, good. Good to go. So, they put six microliter spots on a plate. And then ran it into an uncontrolled lab for mass spectroscopy. Experiment was a disaster. They got nothing useful. Like, okay, back to the drawing boards. Unfortunately, a week later, they were cleaning out the lab, routine cleaning. And for some reason, actually what happened is the autoclave was working, it was busy at the time. So, the person put the plates back in the incubator. Went back to clean out the incubator and saw the plates. Which were overrun with Bacillus anthracis colonies. As you can imagine, this was a Friday, of course. Afternoon, 430. You can imagine how that weekend went. So, for people who don't know about MALDI, it's pretty simple. The plate's about the size of a matchbook. Usually, we're using like a 96-well plate format. You dotted the material on there. You put a polymer coating on top of it. And the laser literally vaporizes one of those spots. Runs it through an accelerator. And so, you've got the proteolytic cleavage products are being accelerated down to this detector. And you get a pulse that's corresponding to the size of the fragments. And the thought is that you can actually identify a bacteria down to the species level based on that proteomic fingerprint. The problem was, and thought it all the way through. No formal risk assessment from the organization. They only did recombinants. Which is why I was talking about an institutional biosafety and then some other organization. Sorry about that. If your institution only looks at the recombinants, all of your pathogens that aren't recombinant skate. So, they did some things that went wrong. And biggest thing was, the assessment never considered it outside of the lab. We always figured somebody would get hurt inside. Something for you to consider. What are you going to do if your assessment is flawed? And whatever you're working with gets out? Do you have the resources? Do you have the occupational health resources to make that work? Mercifully, we never found anything that grew. But we had to figure out who was there. This was an uncontrolled lab. No locks on the door. No card key access. People came and went. There were access controls to the corridor. But not the room. In the end, we figured out about 65 people were at risk. And then we had to recruit enough staff to be able to do it. Mercifully, this was a federal institution, a public health institution. We could get epidemiologists and physicians. And some were the same. To help identify that staff and then treat them. Do you have the ability to scale up? What do you do when it overwhelms your institutional resources? Because it can happen. It did happen. We made some changes. And our occ health people were absolutely essential in that. We had to figure out how to handle this full-scale event that involved the entire campus. And external relationships. Where do we send people? You may have one with an emergency room. Great. Send 60 people to an emergency room. It doesn't work. So you'll need that information. And actually, the question about doing this based for military on post-exposure, it doesn't change. You go back and do the risk assessment. Where were you? What were you involved in? Where were you physically? Where was the material physically? Was this a chronic infector or an acute? If it's an acute, do you have antibodies, residual antibodies? Can you prove that there was an exposure? So it doesn't change whether or not it's being done inside an academic institution or outside 30 years ago by military. Same basic procedures apply. And the occupational health professionals have an integral role in this. And if they don't, they need to. You need to be involved, because if you don't understand the events, we're going to fail. Oh, dang. OK. I hope that helped. And if not, contact us. Thank you. Thank you. I'll go to my thing. I'll go to my thing. I'm hoping it. Hm? Yeah, they don't call them containment levels. It's not. Yeah. OK. Do you think it met the needs? I don't think it did, but it said. I mean, some people that I know had a 12-day post for 12. Yeah. Yeah, no, I had no doubt about that and no issues with the fact that people had to leave. You want to text him. He wants your contact information. Yeah, no, fine. Absolutely. Yeah. Yeah. Yeah. Thank you. Oh, thanks for coming.

occupational health

biological exposures

collaboration

dialogue

worker safety

partnership

communication

risk assessment

biosafety