Inaugural NanoEHS Webinar

Inaugural NanoEHS Webinar

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>> Good morning, good afternoon, and good evening to everyone and thank you for joining today’s webinar, What we know about NanoEHS: How it all begin. My name is John Howard, and I am the Director of the National Institute for Occupational Safety and Health and I have the pleasure of moderating the webinar today. The NanoEHS webinar series is an important platform for agencies participating in the National Nanotechnology Initiative.

It allows us to share information on nanoEHS research, progress, and findings. Before I introduce the panel, l would like to give you some background about the NNI’s nanoEHS research agenda and why this topic was chosen to inaugurate the 2021 series. First, the Federal Government’s commitment to health and the environment has been a central part of a nanotechnology research framework since the early days of the NNI. The creation of the interagency Nanotechnology Environmental and Health Implications Working Group or NEHI, under the NNI was pivotal in charting a path forward to address key nanoEHS research questions. The 2021 NanoEHS webinar series will focus on sharing what we have learned about the environmental, health, and safety aspects of engineered nanomaterials in the decade since the publication of the NNI NanoEHS Research Strategy in 2011. Throughout the series, experts will share the big take-home EHS messages in six broad topic areas with the broader nanotechnology community and will highlight the NNI's role in answering research questions in each of those areas.

This first webinar in the nanoEHS series brings together four pioneering scientists who were pivotal in the emerging field of NanoEHS in the early days of the NNI. We have asked our speakers to share their perspectives on how it all began and to discuss the robust community that has developed and continues to support current and future nano-EHS activities. Today we're going to hear from Gunter Oberdorster, professor emeritus in the Department of Environmental Medicine, University of Rochester.

Gunter’s work has focused on the potential health implications of ultrafine particles, and investigation of the biokinetics and translocation pathways of inhaled engineered nanomaterials. Second, Dave Rejeski, is a visiting scholar at the environmental law institute. Prior to joining ELI, he served as the Director of the Science and Innovation Program at the Wilson Center.

He also worked at the White House Office of Science and Technology Policy, the Council on Environmental Quality, and EPA. His work focuses on the interaction of public policy with emerging technologies. Third, Andrew Maynard is an Associate dean in the College of Global Futures, at Arizona State University. Andrew is a scientist and an author whose scholarship focuses on emerging technologies, and their responsible and ethical development and use. Trained as a physicist, Professor Maynard's work cuts across areas of expertise ranging from the natural and social sciences to the humanities, policy, science communication, and the socially responsible and beneficial development of emerging technologies.

Fourth, Vicki Colvin, professor of engineering and molecular pharmacology at Brown University. Vicki's research focuses on the synthesis and characterization of nanomaterials. Her interests include studying the potential application of nanoparticles for water purification and how nanoparticles interact with living systems.

In 2006 she pioneered the use of water-soluble quantum dots in biomedicine. She served as Brown University provost from 2014 to 2015. So welcome, all four of our wonderful speakers. We have reserved time for your questions that you can ask to the panel. And what I'd like you to do is to type your questions in the Q&A box. Please, try to refrain from putting them in the chat box so we can concentrate on one particular source, the Q&A box.

We'll try to get through as many of the questions as you have with the panel as we can in the time allotted, which is 90 minutes. And I look forward to a lively conversation. A final comment before I turn it over to Gunter. I hope that you will join us for other nano-EHS webinars in the series.

More information on all the NNI public webinars can be found on You can also follow us on Twitter at NNInanonews. And now it's my pleasure to turn it over to Gunter. >> GUNTER OBERDORSTER: Thank you, John. I can't see the whole screen. I will try to get the -- up here.

Well, I hope you can all see the screen so far. I'm trying to get a different view here. >> JOHN HOWARD: We can see your screen, Gunter. >> GUNTER OBERDORSTER: Yeah, but I cannot see the right side because -- okay.

So thank you again and thank you also Stacey and Rhema for selecting me as a panelist for this webinar. It's very nice. And I was asked to talk about my encounter with nanotoxicology, and you look at this sentence here, from accidental descriptive observations to sophisticated mechanistic and translational research, that basically summarizes my dealings with nanotoxicology.

And I'll start with the accidental descriptive observation that was in the middle of 1980 when I was at Rochester, I joined Rochester then. And I worked with Dr. Ferrin, who was a refugee from Czechoslovakia in the 1960s, and had developed a technique to determine lung clearance in rats.

And what he used was titanium dioxide aerosol, micro-titanium dioxide 215 nanometers and bigger. And that was a very nice technique to determine how inhaled toxicants might affect particle clearance. At the time I was visiting a friend in Germany and he worked at the Gusser, formerly Gusser Company, and I told him about our studies.

And he said, oh, we also make titanium dioxide, but a very, very fine one. I became interested. And he gave me an account of where to find nanotitanium dioxide. And back in Rochester, he also had given me aluminium oxide and other ultrafine materials. And back in Rochester, Dr. Ferin, and I compared them size by size by inhalation in rats to see what differences there might be.

And the next slide. What's going on here. It takes a while.

Hmm. No, that's not right. I'm not sure why I can't advance the slides when -- >> JOHN HOWARD: It looks like you're in another program, Gunter. Maybe if you can get out of this program. >> GUNTER OBERDORSTER: Yeah, back to the first slide.

That will do the trick. Here I will go to the next one. There we go.

Okay. Maybe I just had to use the mouse. So then we did this study, this inhalation study comparing size by size, ultrafine and fine TiO 2, we were surprised to see there was a big difference in terms of the reactivity of the inflammatory response that we saw in animals. So the question is, we put down two companion reports in the journal of Aerosol Science, and the basic overall conclusion, results are down here. Comparing the ultrafine and fine TiO 2 and aluminium oxide, which at the time were called nuisance particles, of course, not anymore, because the thinking was that they would not induce fibrosis. Any way, so we saw that the toxicity of the ultrafine particles relates to the larger surface in mice and increased into spatial access, and also the particle surface area rather than the mass should have been the proper dose metric.

Other surface characteristics, physical-chemical ones may modify toxicity. So these were our results. And at that time, the 1990s. So that was 1990. In 1990, there was many studies came out here. And I use these studies that came out, they were done in they were using very high doses of concentrations.

We use the Gartner hype cycle of nanotechnology and translated that to the hype cycle of nanotoxicology, and that starts with the trigger, that is the effects of biokinetics of nanoparticles in the '90s, and there were many of those, and that resulted in a lot of misconceptions to inflated predictions about what was coming out. All nanoparticles are toxic. So it was corrected, and it went out to what I call the trough of disillusionment, the appreciation of reality, which was followed by the slope of awakening, which is leading to increasing insight of nanotoxicology concepts, and then, finally, we are at a level of accomplishments in terms of realistic assessment of hazard and risk. Going on. I'll give you a couple of examples of what I call proof of principle or hypothesis-forming studies that were published at that time here.

And led to this assumption that all nanoparticles are toxic. And this, for example on the left, nanoparticle sunscreen can kill brain cells, that was picked up by the media, here for example, in the Munich Daily Times, it was coming out with the headline, "Sunscreen may soften brain.” That was an in vitro study, very, very high doses given in vitro.

In vivo studies silica and titanium dioxide causing pregnancy complications in mice. And if you look at the doses they were using ___ titanium dioxide and silica dioxide intravenously into pregnant mice, which is equivalent to about 2 grams intravenously into an expecting woman, so you can imagine that's not very good in terms of how they come out, the offspring. And I asked a friend of mine in Germany- he likes to draws cartoons, to draw this one here to find out the exposure [1:16:50], dose and response in terms of how that exposure takes place. So, it starts with two eggs, one normally incubated by a hen, the other cooked, at 100 degrees for three minutes, the incubation for three weeks at 70 degrees, then the outcome is very different.

That is, what happens of course, with toxicology as well, that the dose makes the poison, as we know since the seventeenth century from Paracelsus. Not only the dose makes the poison, also the dose makes the mechanism, which should always be considered. Now _ Vicki Stone and Ken Donaldson, and myself, we published a paper on the history of nanotoxicology. And as you can see here, there are many subspecialties that go into nanotoxicology, for example, the fiber toxicology, the role of particle shape in biotransformation processes. The role of analytical imaging for the subcellular fate of particles and so on.

Like virology at that time. Certainly__the role of viruses as models for interactions of nanostructures with cells and as nanoplatforms in medicine. And then the deposition studies and models, which are -- normally we have nice deposition models. And also the ambient PM issue, the role of small particles and systemic effects. That's all involved in nanotoxicology, and is a precursor, and we subsequently published, with my son and my daughter, my son is a toxicologist, my daughter is an ecotoxicologist, a paper where we pointed out the emerging issue in nanotoxicology based on the study of ultrafine nanoparticles.

And the following, one of the figures we had in that paper was the biokinetics nanoparticles here, different exposure media in the air, it will be used intravenously, and in food and water. And then in general, as we see, the blood is a platform for distribution, inhaled nanoparticles throughout the organism here. And transportation rates are very, very low.

But of them have specifically, what we are interested in -- and we will come to that at the end -- is the central nervous system. When particles interact -- they translocate to the central nervous system. The next slide shows a question that we had. Do ultrafine particles induce adaptation following repeat inhalation? And we used a particle polytetrafluoroethylene which we have found to be the most toxic ultrafine particle that I have ever seen. We had 50 microgram exposure for rats for 15 minutes results in a lethal exposure and rats will die.

So what we did is we had three groups of rats, and that’s what we called adapted, nonadapted and controls. And we adapted them for three days, exposed for just five minutes to the 50 microgram per meter cubed PTFE, and on day four, they received the lethal 15-minute exposure. Nonadapted were sham exposed for three days and then on day 4 side by side with the adapted animals for 15-minute exposure and the controls were always exposed sham exposed throughout. And the results were quite interesting.

In that the nonadaptive animal all died within three hours. And the adapted animals, looking at the lung lavage, In terms of the neutrophils and proteins like controls- no significant difference. They all survived.

And that had to do with the __of antioxidants, that [ off mic ] caused the contractive mechanism in those animals here. So the next slide. Let's go to the final -- and that is translocation to the central nervous system. and this shows what is known for rodent brain pictured in the mouse brain here. There are two basic pathways, neuronal pathways, one is the olfactory pathway from the nose to the olfactory bulb.

And the other is the trigeminal pathway, in the pathway here, from the nose and oral cavity along the trigeminal three branches to the trigeminal ganglions, into the brainstem here. The question is, how does -- how can we translate or extrapolate from rat studies, from rodent studies to humans? This compares the human and the mouse brain. And as you can see, the tremendous difference is the relative size of the olfactory bulb. So in the rat he it's pretty big, and in the human, it’s a small size and there's a lot of trigeminal ganglion present in our species. And we went out to find out if indeed we know for rodents, for mice, in particular, but rats as well in terms of translocation, can that be verified in humans as well.

And -- we published a study -- a review study tissue- specific fate of nanomaterials by advanced analytical imaging techniques review. And the key author here is Uschi Graham, but I should also mention Alan Dozier. He was very instrumental in getting these studies going.

He is at NIOSH in Cincinnati, and he has the wonderful ultrahigh resolution instrumentation to find nanoparticles in tissue.So the high resolution scanning –transmission electron microscopy together with EELS to study the origin and fate of ultrafine particles in rodent and human tissues. And here is a figure here, the human olfactory bul., And there's a small particle pictured

here and here. And enlarged the picture again here. As we can see here in this particle here, there are occlusions, just tiny, tiny particles, just one to five nanometers in size. And they consist of metals. And the next slide.

Shows you an EDS map spectrum. Showing the different metals that are in this insert here. And they consist of lead and zinc, copper, manganese and the form that we thought, a Trojan horse mechanism, introducing those metals into the human brain via the translocation into the olfactory bulb. And so just to finish that up here.

We show a picture of the Trojan horse, it happened at the time people moving with horses, the deadly inserts into their town. That's the part I wanted to tell you very briefly and I look forward to your question. Thank you. >> JOHN HOWARD: And thank you, Gunter. And if you can take down your slides, we're going to go to Dave Rejeski, next. Dave, do you want to present your slides? You're on mute if you can come off mute.

>> DAVE REJESKI: Can you hear me? >> JOHN HOWARD: Yes, I can now. >> DAVE REJESKI: Can you see that? >> JOHN HOWARD: Yes, if you can just hit slide share so we can see the slides better. It looks like your slide share is way over to the right. Not quite as far over to the right. >> DAVE REJESKI: Wait a second. Here we go.

>> DAVE REJESKI: How is that? >> JOHN HOWARD: Yes, that's fine. Thank you. >> DAVE REJESKI: Okay. Perfect. Sorry about that. Well, thanks for doing this.

It's great to be back, with all of the people that I interacted with 15 years ago. I spent some time just thinking about how to do this. And I thought the best thing to do would just go back in time and see if I could capture, because I'm not obviously a toxicologist, just capture some of, sort of the context of what was going on back then. Because I forgot a lot of it. So I pulled a bunch of slides that I actually gave at talks, one was at Harvard and one was the American Chemistry Council was at and I tried to get a sense of what was I talking about, and how is that relevant to anything that was going on contextually? So this was 2005. You have to think a little bit about Bush had won the presidency, Katarina happened.

Tom Brady and the patriots won the Superbowl. YouTube was launched and if you're a Star Wars fan, you probably watched Revenge of the Sith. This was an important point for the National Nanotec Initiative. In 2003, President Bush at that time signed the National R&D Act. It was essentially, an authorization without money.

In 2005, the money started to roll. And this was the beginning of a massive amount of investment by the Federal government. And other governments around the world. Just I think in 2004 we had money from the EPA, and I started doing work, I had some of the first meetings in Washington on nanotech that brought together the toxicology folks with industry, with environmental groups. And so that was kind of my entry point.

And when I was starting to think about this in 2005, one of the things I always came back to was a friend of mine Ed Tanner who has done work on unintended consequences. He says, wherever we have advanced technologies, they promote self-deception. I began to ask myself, how could we possibly deceive ourselves here? And what could go wrong? And that led to a whole bunch of questions about what some assumptions might be.

I think one was that the public would accept this as markets expanded. You probably heard already there were things coming into the marketplace. And those were getting up by the popular media. The NGOs would remain supportive and passive. No. I had some very interesting meetings with the ETC Group, Friends of the Earth.

For them, this was an incredible opportunity to sort of say, now, we're releasing another set of engineered materials into the environment, we're putting them into our body. They took out the old playbooks that they had essentially perfected for GMOs, and they launched again. And they were incredibly good at messaging and getting the message across to people far better than I was or the government was. I didn't agree with their message, but I often applauded their capacity to get it out there. So these folks obviously were kind of coming into the space and coming in fairly aggressively. Press coverage would remain fair and accurate -- no, you saw what happened in Germany with the Taga cycle, and how they picked up on the science.

The other thing was that the traditional press, would they even matter? Where were people getting their information? 2004, Michael Crichton publishes Prey, which is about a pretty scary nanotech story. It was on the New York Times best-seller list for 14 weeks. It didn't get made into a movie, which we predicted probably 20 million people could see it, based on the box office-draw of Crichton’s movies. In 1986 there was a book that came out called Engines of creation by Drexler and proposed the idea of self-replicating programmable nanobots; this gave rise to the kind grey goo scenarios that were going to eat the earth. 2004 Spider-Man Doc Ock used nanotech. So what people were getting messages from was popular culture.

And these were scary messages. It goes back to the Kai Erickson at Yale, a sociologist studied the public's perception of new pollutants, and they called them new species of trouble. And nano had the potential to be an new species of trouble when I was looking at it at that point in time.

And the messaging was coming from multiple sources, not just from scientists. There's this issue of, could you make analogies from sort of macro, microscale to nanoscale. There was this whole novelty thing. At one level, people were getting the message that this was incredibly novel. We could create whole new materials, which we did. We created multiple forms of carbon.

We could take a material that was inert and made it reactive. We could create this incredible amount of novelty, and they asked, does that mean new risk? it was a logical step, a logical question that people were asking. And all this stuff we know about at the macro and microscale forms of the chemicals could say anything about what was going to happen at the nanoscale, so I think that was an issue. I think it was interesting. Can we assume away the existence of black swans; these were low probability, high impact events, and we've kind of stopped talking about that, but that was part of the discussion in 2005. Could these nanoparticles be used offensively in weapons systems? Could there be some sort of spill or release? In the background, there was this sense that something could go wrong, and it would be sort of a high value and high impact event.

And were we prepared to deal with that? We ran the first sets of public perception studies in 2005. We sent people all around the country. We did these year after year for seven years. And these were some of the first kinds of messages that came out of these studies.

One was, the genie was out of the bottle, and this was repeated again and again in future studies that the technology development curve was sort of outpacing our capacity to understand the technologies. And their impacts. We were essentially running after the train and this train was being pushed by massive amounts of investment, power and politics. It became kind of a national prestige technology for the US. So this message never goes away completely.

The second one is, can we trust industry? >> JOHN HOWARD: Dave, this is John Howard. I don't think your slides are advancing on the screen. >> DAVE REJESKI: Ah. They are here. >> JOHN HOWARD: Well, we have a number of people in the chat box that have asked about the slides working. And I personally only see your first slide.

>> DAVE REJESKI: Well. Okay. >> JOHN HOWARD: You may want to go out come back again and see if you can advance them. Ah, now, I see the second slide, I think.

>> DAVE REJESKI: Can you see it now? >> JOHN HOWARD: I don't see anything on the screen right now. Now I see I think it’s the second slide. >> DAVE REJESKI: Can you see it? >> Can you try to advance it? >> DAVE REJESKI: Yeah. Now, I can't get it to work. There we go. >> JOHN HOWARD: There's just a lag.

There's a lag time in this system. So it's starting to come up your -- I guess it's your third slide is starting to come up. >> DAVE REJESKI: Yeah, this was -- I went over these assumptions, right? Can you see those John? >> JOHN HOWARD: Yeah.

Okay I think all the bullets are maybe completed. No, there's one more. >> DAVE REJESKI: All right. So let me go on. This was the public perceptions.

Can you see this one? >> JOHN HOWARD: Yes. >> DAVE REJESKI: Okay. Good. So I went through the first one, genie is out of the bottle, the trust in industry, I don't think it completely evaporates. There was also this issue of trust in actually the regulatory system. Can we regulate when we actually don't know what's going on? How many people actually know? And I think the last one, which continues to plague the field was, would the regulation even work, these regulatory systems.

So we did a lot of analysis of the various regulatory regimes, the FDA, EPA, all these agencies and drilled down on a lot of the regulations, and certainly some of them were 20, 30, 40, years old. And so there was this question about, do we need new regulatory systems? It took ten years to update the toxic substance control act, for instance, to deal with some of the issues around nanotech. So these initial public perceptions don't go away. The trust in industry, and trust in government oscillates over the years. But this issue of, is the technology moving faster than our understanding, are the products coming out into the market before they can be properly studied? Can we regulate them? Will we regulate them, and who is going to regulate them, I think those continue to be part of the conversation. The other -- I want to make another thing is we weren’t alone.

By this time, investors, I gave talks to investors who were trying to figure out, should they do due diligence and could they invest in these companies. And also insurance companies who had to calculate the risks. So at that point in time, you know, 2005, people were talking about 300 to 500 products in the market. We took over a database, at the Wilson Center from the federal government- they had about 260 products about a year later. These were products that ostensibly used or somehow used nanotech. There was also I think a reality gap.

When people heard about this from the government, they heard about cures for cancer and super-efficient batteries. And paint-on solar cells, and what they saw were socks with, you know, essentially nano microsilver in them, or tennis rackets or cosmetics, teddy bears, right. So there was this kind of disconnect. And I think we never communicated to people very well about how long it takes before you go from initial investment in science and engineering to actual products, to actual applications. This was the interface between nanotech and the public, the products, we bought lot of them, and we had Wilson Center fashion shows and all kinds of things that we did with these. And I think this was kind of an interesting library of where nano was actually appearing.

The investors were interested in existence of research, some of which was showing negative impacts, this issue of, can nano go across the blood-brain barrier, some medical people were thrilled by that, they could deliver drugs to the brain. But the research -- the research that’s out there is often misinterpreted by the press and blown out of context. Level and adequacy of government funding for health and environmental implications research.

It was pretty low at the beginning and we spent a lot of time going back and forth with the government about how much they were actually spending. Would the regulations work, and was there any kind of comprehensive public engagement strategy to deal with these public concerns? Is it working, John with the slides? >> JOHN HOWARD: Yes, sir. >> DAVE REJESKI: Okay. Good.

This was a big issue for companies. You know, my friends in intel didn't like this slide. But was it an asset or a liability? Should the companies who are putting this, or using this talk about it? Was this going to affect their market status? Was it a propellant, was it a barrier, a hurdle? It depended on what country you were in. I think probably in Japan, it was probably an asset.

It wasn't clear whether it was an asset in other countries. So this was a game we developed called Nanopoly, get your product to market. And it was just a sense of just how complex this was. How many actors were in the field. What could go wrong? People were talking about, should there be a no nano label? What would that mean if you had a product out there on nano? What if we start putting nano into food? What kind of response would that trigger? What if there was a nanoparticle spill, how would we get the particles back? So it actually became very interesting to play through different scenarios. And I found in a lot of the talks I was giving, I was talking a lot about the need to game- the system, sort of think about what scenarios would happen, because there was so much certainty.

Think about what failure meant, modes would happen, think about bad as well as good. Have multiple scenarios, think about hedge strategies, so you came out ahead even if something bad happened. There was a need really to push risk management strategies to other players.

We did a lot of work with small businesses and startups, who had no nanoEHS folks. No one was responsible -they had one-eight of an FTE. And yet they were very concerned, at least, you know, about what were the implications of this. You had places like Berkeley, California, Cambridge, Massachusetts, who were starting to regulate nanotech. There were all these players, and it was just a mess. It was like a huge mixing bowl.

And when I first started working on this, it was, how do you get all these people to talk to one another, how do you get the right information to the right people at the right time? How you move impact assessment upstream? How you bring together the people essentially who were doing the development with the people downstream that might be regulating them or trying to figure out what the damages might be, so design for environment. There wasn't a clear message. You know, I think there's a much clearer message now. But there wasn't then. There was no real public engagement strategy.

Everybody was kind of going it on their own. At that point in time, you know, I basically, I was paranoid. Now, not in a bad sense. But I do think when you're dealing with technologies like this, and you're starting to introduce them into society, paranoia is actually useful, it forces you to focus on what you know and what you don't know. It becomes somewhat humbling and forces you to think about what you can control, and what you can't control.

When I moved from nanotech to synthetic biology, I became more paranoid. But I always found this was kind of an interesting sort of approach to how do we deal with the massive uncertainties when we start sort of introducing disruptive technologies into society? Nanotech project is still up there, if anyone is interested in history, and I will stop there. John, thank you. >> JOHN HOWARD: Thank you Dave.

I appreciate it. And we'll go on to Andrew. >> ANDREW: Thanks, John. Dave, if you can un-share your screen, I will go to share mine. Great.

Just give me a second. Okay. So this is quite a strange and nostalgic meeting, I was just flicking through the participants and it's like a 2000s reunion of everything nano. And I actually feel quite humbled sitting here, because there are so many people on the call that have greater expertise than me and have contributed really important things to our understanding of nanomaterials and environmental and health sciences. But I did want to try and give a personal story as to my background and some of the contributions here.

I would also say one of the things I teach my students when we talk about communication is, you've got to kill your darlings. And this is such a long, convoluted story that I've had to kill a lot of darlings in trying to tell it. So please forgive me if I don't touch on things that are important here. I would say also say in terms of context, I've been trying to get away from nano for a good decade plus now. Most of my research looks at emerging technologies, responsible and ethical innovation, and I deal with much bigger issues, if you'll forgive the pun than the really small stuff with nanotech.

So this is a really interesting journey back into the past for me. So to tell the story, I wanted to start off with this 2004 paper. This was work done in the early 2000s when I really began to get involved very, very specifically with exposure to engineered nanomaterials. So on the left, you see a bucket of single wall carbon nanotube from ____. This was work when we were asked, in the early 2000s, myself, my colleague Paul Barron, by NASA to do some quality control work around some of the work that they were funding around single wall carbon nanotubes.

And we pretty immediately looked at this and thought, the problem is not quality control, but the problem is inhaling those motes of carbon nanotubes that are being released. And that led to one of the first and earliest studies looking at the types of exposure we get from these materials. Really fascinating, this particular set of experiments where the first time we went down to Rick Smalley’s labs, he was incredibly excited about this material. Vicki, you will remember this in the early days at Rice. And he used to get a bucket of this and shake it, so the whole lab was full of these motes. And he was so excitedly pointing them out to us, and I was coming from a occupational health perspective, we were trying to cover our mouths and desperately trying to get out of the room.

Next time we visited, things were very, very different. Rick and the lab there learned really fast about how to think about the public health and the occupational health aspects of these. But as I said, that was the first time that I really deeply got involved with exposure to engineered nanomaterials.

But this was the result of a long journey that started well over a decade before this, with my Ph.D. thesis. So in 1989, I started working on the analysis of what we were then calling ultrafine particles at the University of Cambridge. Using this beast here, this is not me, but this is the beast I did my Ph.D. on, a VD instrument HP501 scanning electron microscope back in the days when everything was manual. And I was particularly interested in how we could use what were then cutting-edge technologies to better understand nanoscale particles that were released into the atmosphere.

So that work, ramped up in 1993, and it was published over the next few years, so, for instance, one of the things we were able to do there was to apply what were then very unique techniques to try to understand the elemental composition of very, very fine particles, collected from the atmosphere. What was particularly interesting, though, was I was in a research group that were particularly interested in heterogeneous catalysts. So they were using these microscopes to study intentionally designed just a few nanometers in diameter, and to try and understand their catalytic properties. So this was back before anyone was talking about nanotechnology apart from people like Eric Drexler but the materials science world, we were already engineering materials at a nanoscale in order to try to do things differently. Also as a part of this early research it exposed me to over 100 years of work around nanoscale particles and ultrafine particles. So this is just one example.

And aerosol scientists among you may recognize this, and this was from a paper by John Aitken in the 1880s, where he was studying, measuring nanosized particles in the atmosphere. Of course, he didn't know that they were nanosized particles, but he was actually measuring concentrations of ultrafine particles and he was using a device that is still the basis of how we measure these concentrations today, a condensation particle counter, and I mention this because this was actually part of my dissertation back in the early 1990s, looking at this 100 year history of these measurement instruments, but also it was a really important reminder and touch point that we have been studying and measuring nanoscale particles for a long, long time now. And it's only recently that we started categorizing them as ultrafines or nanoparticles and getting particularly excited about them.

So that was my dissertation. At the end of it, I was told really interesting, but nobody is interested in nanoparticles, so I started studying much larger ones but came back to trying to delve into exposure of ultrafine and nanoparticles towards the end of the 1990s. This resulted in, I think still one of the first institutional reports around occupational exposure to ultrafines and nanoparticles. And it still hasn't been declassified by the Health and Safety Laboratory in the UK.

But I put this up to give you a sense of what we were looking at. This is a study that we did late 1990s, to try to understand occupational exposure to nanomaterial. You can see we use this very quaint phrase at the time, nanophase technology, which, of course, everybody else began to start using it as "nanotechnology." But I put this out just to flag that even in the 1990s, we were beginning to ask fairly serious questions about exposure to these fine particles, and the potential health impacts. A lot of that came together in this workshop hosted by the Royal Society in 2000, looking at ultrafine particles in the atmosphere, but if you look through those papers, you begin to see how people were beginning to put together different aspects of research to understand the nature of nanoscale materials and their potential impacts on health. Gunter has got a really important paper in this collection and a number of other people.

My contribution was looking at a range characterization methodologies which are still used today. So from there, I became increasingly interested in exposure to these nanoscale materials, whether they're intentionally formed, or whether they're incidentally formed. And one of the really important things I will still stick to, that I think sometimes there is false dichotomy there between different kinds of nanoscale materials. One of the things that came out of this was the first international symposium on occupational health implications of nanomaterials. This actually came out from an ISO Working Group that was responsible in the 1990s for standards around occupational exposure to aerosols, and in the early 2000s, we began to look at nanoscale materials, and we decided as we looked at this we really needed to bring expertise together, and this ended up with this first conference back in 2004. Moving on from there, I began to get more and more interested in what was happening with nanotechnology and nanomaterials more broadly.

And this is where I started working with Dave. You saw this image in Dave's slides. This is part of the collection of consumer products that we put together that claimed to use nanomaterials or contain nanomaterials in some way. I put it up because it also appears in this paper that was publish in the 2000s where I began to pull together a lot of different streams of thinking here. Not only looking at the health and the environmental implications of nanomaterials and nanotechnology but how you fit that into a broader research context. And that's right about the same time fed into this paper which is still a fairly significant paper, and you'll see a number of names there, including Gunter, including Vicki, where we brought together a group of people, and, again, this was under the direction of Dave Rejeski to ask, what are some of the really big research questions that have to be asked here? That was in 2006.

And John, just for your reference, that is my hand in a NIOSH laboratory, playing around with single walled carbon nanotubes. So there was a NIOSH connection there. This was an important paper, because we began to identify what some of the big questions are that we have to address if we're going to get nanotechnology right, and by right, I mean that we see the societal and economic benefits of it. At the same time, we don't create something that's going to create more environmental and health harm than we really want to see.

So that was back quite a long time ago. And as I said, I've moved away from nanotechnology and looked at much broader things. But I still keep tabs on what's happening, and one thing that's interesting to me is while research into nanoEHS has continued, there seems to be far less debate about what's happening in the real world. So, for instance, in 2016, I wrote this piece for nature nanotechnology about the material, Vantablack, supposedly the blackest material ever. And what intrigued me about this, and you still see this, this was a company that was very excited about spray on carbon nanotubes, they were basically using it as a paint.

And they were putting it onto different products to create this incredibly black surface. And I remember in the early to mid-2000s when we were talking about potential uses of nanotechnology one of the things that a lot of people in the field said was an absolute no, no, was taking a material that seemed to have asbestos-like properties and aerosolizing in a way that people could potentially be exposed to it. And yet here in 2016 was a company doing exactly that and the only press coverage I could see was people getting excited about how black it was. There was no conversation at all about the potential environmental and health implications. And that actually worried me. Because it made me begin to wonder whether even though we're doing all this research into nanoEHS it's not actually translating into decisions around products.

And just to emphasize that, I actually came across this in my bathroom just a couple of days ago, a spray cleaner for glass surface, and there right on the front of it, you've got nanotech protection, cleans and protects. And so this leaves me with the question, what are we doing, what have we achieved, is this product out there because we've solved all the problems around nanomaterial exposure? Or the regulations are there? Or is this product here because despite all of the research that's been done and going on, nobody is really caring in the real world about what's happening? And with that, I'm going to hand back to you, John. Thank you. >> JOHN HOWARD: Thank you, Andrew.

Thank you for that last product placement there. So we're going to turn to Vicki now. >> VICKI COLVIN: Great. So I will go to the board. Share screen. Can you see my screen? >> John HOWARD: It's coming up.

All we've got to do is hit “slide share” -- there it is. Thank you. >> VICKI COLVIN: All right. Great. So, tt's a pleasure to be here and I'll certainly echo what everyone else said about seeing old friends and thinking way back into what was going on at the start of all of this, as the webinar is called.

And I just want to thank the organizers for including me. It's been areally eye opening to reflect back, looking forward to the questions, I will do my best to stay on time. So I want to start with where I was in the 1990s. This is a beautiful Ansel Adams picture of Berkeley.

I don't know if you can see my pointer, but this tall structure here just over the left is where the Chemistry Department was, and that's where I did my Ph.D. So I come from a interesting and different background than a lot of folks I got to know in the NanoEHS world in that I am a, you know, ever since back before nanotechnology was popular, I was doing it. So I was trained as a physical chemist looking at nanoparticles. So what you see here on the left are a bunch of quantum dots.

On the left, it’s blue because it’s tiny, on the right, around 8 nanometers, it's red. And these materials were the subject of my Ph.D. thesis. And really ingrained in anybody studying nano in the 80s and 90s, was that the size of a material had powerful, powerful effects on its physical, chemical, magnetic, electronic properties.

And that was the whole reason we studied them. And so from this we published a paper on making light emitting diodes, I was very focused on optics at that time, and I'm the proud owner of a Samsung QLED now, many, many years later. But this concept that you're working in a materials area, you're trying to make cool materials that are interesting, and you know, you might argue whether a QLED solves any problems for people but it certainly is contributing to the technology that we use every day. And that's what motivates a lot of researchers in science and engineering, creating materials for a better world, and that's certainly what I came out of in the 1990s as I started as a professor at Rice University.

So when I started to kind of poke around and I had a lot of contact with the environmental engineers at Rice particularly Mark Wiesner in the early 2000s, and we started to talk about how chemists make stuff that you know, pollutes the world. And that's terrible for chemistry, and I thought, well nanotechnology will never do that. And then I noticed this is an OSHA MSDS website sheet about how to handle carbon nanotubes. And you’ll notice here, I remember when my students brought this to me, It says, “elemental carbon/ carbon black is mainly a nuisance dust.”

That's funny. Carbon nanotubes are not elemental carbon, or we would not have gotten several million dollars to study them from a federal agency. And if you looked at it more and more, and I did, we started to notice that the regulatory systems that were out there were treating nanomaterials like they were bulk materials, and this was kind of my weakening material, where I saw there was a big disconnect, the federal government was just starting gearing up for the National Nanotechnology Initiative but their regulatory agencies were saying, “hey, nano is equal to bulk, which didn't make sense.”

And that got me worried. I think also because I was a chemist and aware of some, you know, chemistry doesn't have a great reputation for managing the products of its research. I sort of developed a slide, I'm sure some fraction have seen this. The Tinker Bell slide which as a technologist, which I consider myself, we develop cool molecules, cool materials that solve real world problems.

And that is what we promise to society. Our funding agencies. We're going to develop these, and they're going to improve the world, and that's part of our contract.

The bad news is that in many, many cases, there are unanticipated consequences that lead to, perhaps, you know, you can argue, what's the balance, but they lead to clean up efforts later in different arenas for a lot of different people. And so I really became aware that if I was writing proposals to the US government, asking for money to do technology development, I better learn quickly how to avoid, the negative consequences that history had taught us happened. And how to do that is kind of the next part of my story. But I'll just say that somewhere around 2001 I became convinced that any emerging technology will present risk, just look at our history, and by "we," I mean the royal “we”, the science and engineering funders people, involved in any emerging field, we are actually ethically obliged I believe, then and now to study and mitigate those risks because we promise good things, which means we also have to put a hat on, and think what bad things could happen. That's not a terrible thing to do, that's actually part of what we should be doing. So I got very high on my horse about that.

And, now, how do we do it? How do you actually do that in a laboratory? My laboratory is making quantum dots, magnetic nanoparticles. How is that going to study risk? The first thing I got to know a number of folks on the call, the domain experts like myself can help scope the risk. We heard Dave talked about the worries of the grey goo, nanorobots in people’s bodies. It didn't take a lot of meetings to say, those are maybe important social conversations, but they are not things I can test in my lab. The quote I developed was, not in this century, maybe next century. And instead we had the more mundane issues of how are we going to dispose of nanomaterials that might be in quantum dot lead LEDs, and what are we going to do about nanoparticles in consumer products as you heard Andrew talk about.

And that was really going to scope the risk for this particular emerging technology. Then you make reasonable hypotheses. This paper in 2003, boy I got so much negative commentary on this paper from my own community. But what I did in the paper was simply lay out, there's a couple of papers we published at the time about some general reasonable hypotheses for why we might think engineered nanomaterials could present environmental or human health issues, maybe, possibly. And ways we might test them. And you know, what was interesting that I'll share is that the community, the nanotechnology community that was pushing it, the NNI folks, were not all that happy.

Because they're like, well, you have no evidence that there's something bad. You're going to go out and find evidence. And I was like, you know. There was a lot of discussion, in fact, Rick Smalley pulled me aside one afternoon after reading this and said, you're just throwing gasoline on the fire. And he meant the concern that people had about gray goo that Dave was talking about. The nanotechnology didn't want necessarily anything to do with this.

Lucky for me, there were a lot of talented risk researchers out there who had been studying inhalation and nanotoxicology and that community was really ready to step up and become involved. So we, at Rice University, through 2001, started a large center that I had the good fortune to direct for over a decade which really centered in part on environmental implications of nanomaterials and also had a large focus on nanomedicine. So of course, human health interactions. And we tested hypotheses, we started to actually red team it. How could nanomaterials be the most dangerous things? We learned somethings in that in retrospect would seem obvious to a lot of people.

In the carbon nanostructures, the more hydrophilic, the more water soluble those systems are, the less acutely toxic they can, for interesting reasons. And also in the quantum dots, back to the TV screens, if those particles dissolve and release cadmium, they're extremely toxic to environmental organisms. So a lot of safety by design in both of these systems is through manipulation of the surface of the nanomaterial leaving the core material the same.

And there's a lot of great work from many talented groups focused on safety by design on nanotechnology that really centers on how do you prevent unwanted acute toxicity, and chronic toxicity if you have information about the material, and how it might be used. And so what I can just conclude in this section, second message is you really need the domain experts in the complex risk ecosystem discussions, and they may not want to be there, depending on how the field is developing, and what the risks might be. I think in nanotechnology, that was a slow uptake. And eventually, it now accepted and readily looked at by the nanotechnology community.

But it certainly was not at first. It was definitely seen in a negative light, in part because of the public conversations that were to many with be threatening the development of nanotechnology. That was their perception. So sort of using the discussion of risk is a balance, not everything is dangerous, not everything is safe, is sort of the goal. And I think in particular, the development of safety by design, that sort of made it a lot easier for people to manage on both sides of the fence.

And finally, as a critique, what does quality risk research mean for an emerging technology? Dave sort of alluded to this, but what do you do when you have a technology that's not even in existence, how do you worry about the risk? You worry about all the good things you can do with it, so you can certainly make hypotheses about possible risk. But it's really hard to do. And as I got to know the community of EHS researchers better, what I realized is their comfort zone is in dealing with known materials, known products, known exposures, that’s something they can get in there, they can measure, they can assess the risk and they can ideally mitigate it. When you're dealing with nanotechnology in 2000, it was not really clear what materials were going to be out there.

I mean there were already consumer products as we found out later that were there. But there was a lot of uncertainty in the area and trying to fit the normal paradigms of risk assessment which involve a lot of specificity onto this very amorphous area was problematic. And I think that continues to be a challenge for nanotechnology and for anyone looking at the risk of emerging technology is how do you do it before the technology is fully baked? And of the option of just saying, “eh, we're not going to worry about it until we have a product takes us back to the 1940s. So you don’t want to do that.

That remains one of our goals. And I will give you one concrete example to end with. I have this debate on so many conferences on nanoEHS, and I'll share it with everyone, because it's emblematic of this early stage versus late stage risk management. So what you're looking at are some pictures of commercial nanoparticles, the one on the bottom is materials that we took ourselves from commercially available sunscreens. And, you know, as a nanotechnologist you can see the top one is silver, it's very, very polydispersed, lots of different sizes, the bottom one again, it's kind of a mess.

And I can take these materials, and I can study various environmental or biological effects of them, but I'll only learn something really specific about them. But, on the other hand, they might be similar to what's used in products. They could have relevance.

So some of the community wants to study things like this. Of course, I am the chemist so I'm going to make beautiful nanoparticles that are precisely controlled, and this is what I am going to want to study, because it gives me a sense of, where will I find materials that are particularly dangerous or particularly safe? So this very fundamental question of what you study is actually at the heart of how we do early stage work. So what you see here is actually some, in this particular case of antimicrobial studies of lots and lots of different nanoparticles, we're going to libraries and big data to get better handles on the trends. But the simple picture shows you, if you want to make something really toxic to microbes, here's the structure you adopt, if you want to make them less toxic, here's this other structure.

I think that's an important issue because none of the particles here are necessarily the ones that might be in products. Which brings up the issue of knowing what is actually in products, which we still don't clearly know. In any case, that dichotomy, between specificity and generality and how that fits is one of several that you'll find in the sort of perspective and philosophies of what does it mean to do risk research in a really young technology area? So my final thoughts, I continue to think, especially as I see new technologies develop, artificial intelligence, CRISPR, the scientific community, the funding community is absolutely obligated to evaluate risk, and not wait until everything is fully defined. So we have to solve this problem more broadly, and I mean the big “we. “ It's going to be important that the people who develop the technology are in the room and actively involved, and haven't outsourced it to the risk researchers. That leads to a lot less impact and a lot less influence on what gets developed by the folks making the technology.

So finding ways to pull them in, and keeping them engaged is important. And, finally, just putting it out there, what you do for risk research in early technology is going to look a lot than late. That's an ongoing question. Thanks everyone and I look forward to the discussion. >> JOHN HOWARD: Thank you Vicki. Great presentations, all.

And I want to thank all of our presenters. I wanted to start out with a fairly large question. It has to do with the interaction between research, whether it's intramural by federal research, or extramural funded in academic centers, and the relationship between research and regulation. We have now, other than Andrew's 1880s historical anchor, we have had probably 30 years at least of looking at nanotechnology and nanomaterials, and when we look at the regulatory agencies, which are members of NNI and NIHI on the environmental side, EPA, on the consumer side, the Consumer Product Safety Commission. On the workers side, the Occupational Safety and Health Administration, how does the panel think that we have done and the "we" here is NNI and all of its member agencies, including extramural researchers in giving to regulatory agencies the kind of science that would lead to the ultimate goal of risk evaluation and looking at the implications of a particular exposure to consumers, to the environment and to workers that would control those types of exposures in national regulation.

So I'll start -- let's go in reverse order. We'll start with Vicki first and see if you have any thoughts on this. >> VICKI COLVIN: Yeah, my experience is, I think it's been great to have FDA and EPA involve. And my only, you know, my wish is that they could be more involved. I think at the end of the day, the primary funding for the academics is drawn from NSF, NIH, larger agencies. So the ability to really connect up.

And I'll take the silver example. I'm really motivated to connect. Because if we could predict silver dissolution in a lot of environments, then you have a sort of angle on connecting to a threshold and exposure level that you could set in a aquatic ecosystems, but funding that through conventional basic research channels is going to be really tough. This gets back to the problem, regulatory science in general is not strongly supported enough by the federal government, and this is a great example where you really need some research to kind of close the loop between a really huge pile of academic studies that are out there.

And then, okay, how do you take that and sort of turn it into knowledge that's going to influence, hey, if you put silver in X landfill, here's the limits you might face. So I think there needs to be more of it, and what they've done has been really great. >> JOHN HOWARD: Thank you Vicki, Andrew? >> ANDREW MAYNARD: I'm a little conflicted here, John you'll know that I pre-dated you with NEHI group being co-chair when it was first set up. And it was really exciting in those days, and early years, where we had researchers and regulatory agencies at the table. And everybody was focused on what are the questions we need to ask to ensure that products that contain these materials, and these technologies are as safe as possible.

And I think that was an important and unique part of what happened over the last 20 years with nanotechnology, I may be wrong here, and correct me if I'm wrong, I think we've seen a growing disconnect between what happens in the academic field, academic domain and the regulatory areas. And I say this because we've developed a research funding system where to get research funding here, you've got to prove to people, you've got to convince people that there's a problem. If you're a nanorisk researcher, there is no future in you in proving that something is safe. You've got to show that it's risky. And that has led to increasing research where people are scrambling to find the thing that they can show to be risky.

That does not serve regulatory science, regulatory science needs the right questions being asked and the right evidence and data being produced. Not people trying to find the next thing they can prove is dangerous. So somehow we've got to close that loop. I may be being a little bit cynical here.

Correct me if I am. >> JOHN HOWARD: Thank you, Andrew. Dave? You may want to come off mute, Dave. >> DAVE REJESKI: I think Vicki raised an important point.

That is, how do you create a safe space for these discussions to take place between the people -- keep in mind a lot of the academics, they might be developing the products especially newer commercial products maybe in companies. You have to deal with actually, how do you get inside of companies, and would they be willing to share IP with you. We did an exercise, at the end of the nano project which was, we basically got -- at the request of a bunch of large companies that were developing nano-based packaging materials for food. They said, basically can you get a bunch of people together the NGOs, the regulators, et cetera, and we want to have a discussion with them about things that are coming down the pike.

They are not in the market yet. We ran this for eight or nine months. They did it by developing product scenarios.

It was one way to share with the regulators to say, this is what we may be developing, and we'd like to know how you would be reacting to this, what kind of data would you want from us. The regulators got a look upstream and the people who were actually developing the products got a look downstream. And it was pretty useful.

It was all based on scenarios which we knew reflected pretty accurately what was actually there. Though, it wasn't clear what company was developing it, we had to protect that. So we did a bunch of experiments. I did similar ones with synthetic biology. We need a lot more experimentation about how you actually create that dialogue. Because we don't know it.

The typical way of doing it is, wait until the thing is out in the market and have data to analyze instead of being able to say, no, we have to think much earlier. I remember doing some work with a Fortune 500 company. And they basically told me, "Look, they said bad news is good as long as it's early." That's a great bumper sticker. If it's early, we don't have to throw lawyers at the regulators for 20 years.

We haven't made huge investments, we haven't locked in the IP. And I found if you can do this successfully -- it's not easy to do, right -- in the case of synthetic biology, we had biologists go back and redesign their organisms to take risks out of them because they were in a room with ecologists who brought up potential ecological risks. They said, we can deal with that. But that was a much easier dialogue to have when they only had to redesign the organism versus having a product in the market. So I don't think -- I think it's an enormous opportunity to, how do you move the conversation upstream, what kind of techniques can you use? I also found that generally young researchers, young PIs were easier to engage than older ones. I don't want to generalize that.

But some of the younger people especially in the biotech space have kind of internalized this sense that this is a responsibility for us. As Vicki said, that's part of what I'm supposed to do. And they're looking for ways to figure out how they can actually get this actually manifest this and take it into the design process. This ability to upstream, downstream, creating safe spaces. And getting people to actually redesign things. The other thing that's happened that makes this easier is people have focused on -- less in nanotechnical but more in biotech but speeding up the design, build, test, learn cycle.

The faster you go through this, the easier it is to innovate it. In terms of saying, I have learned something bad, now I'm going to redesign. If you're in a very slow DBTL cycle, this is painful. If you're in one going fairly quickly, it's much easier to learn things and put it back into the design.

Retest it, build it, and try again. There's some hope. And this goes back to the idea of using libraries, using robotics, using AI, all of this speeds up our ability to learn faster. >> JOHN HOWARD: Thank you, Dave. Gunter any comments on research versus regulation? >> GUNTER OBERDORSTER: I view this more from a practical side.

And I think NIOSH is doing a good job visiting sites where nanomaterials are manufactured. When I think of Chuck Geraci, for example, visiting those sites. What I'm missing is them to coordinate that better with researchers in terms of doing some toxicological studies, getting the exact material and also the industries are oftentimes reluctant to get people into their facilities. But that would be key to get those materials and testing them. We could even start with simple in vitro studies but then move on to in vivo studies as well. And the important thing is to develop exposure, dose, response relatio

2021-03-20 17:52

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