#214      27 min 22 sec
Toxic titbits? The effects of nanoparticles on our health

Bio-nanoscience investigator Prof Kenneth Dawson discusses current research into nanoparticles and their potential effects on our health. With host Dr Dyani Lewis.

"We tend to look at, really, details, we look at what the surface of the nanoparticle looks like when it's inside a cell. We ask where it's going inside the cell, why it's going there. We ask will it cross a barrier, say a barrier of the lungs, a barrier of the brain, and what would that imply if it did." -- Prof Kenneth Dawson




Prof. Kenneth Dawson
Professor Kenneth Dawson

Professor Kenneth Dawson is Director of the Centre for BioNano Interactions (CBNI), which is the National platform for excellence in the interaction of nanoparticles with living systems, and Chair of Physical Chemistry in University College Dublin. His scientific work has been recognized in award of various prizes (Sloan, IBM award, Dreyfus, Packard, Cozzarelli and others).

His professional roles include participation in the EMEA Nanomedicines Expert Group, membership of the Scientific Committee on Emerging and Newly Identified Health Risks (SCENIHR), participation in the OECD and ISO working groups on standards for Nanotechnology, Chairing the International Alliance for NanoEHS Harmonoisation and co-ordinating several large research projects in the area of nanosafety and nanomedicine, including the EU Research Infrastructure for nanosafety assessment (QNano).

He is currently Editor of Current Opinion in Colloid Science, Senior Editor of Physica, Associate Editor of Nanomedicine as well as Journal of Nanoparticle Research and former President of the European Colloid and Interface Society.

He has extensive experience of leading international research teams at the interface between materials and biology. His recent work has focused on the biomolecule corona that surrounds nanoparticles in biological milieu and how this mediates nanoparticle interactions with living systems. The long-term goal of his research is the development of a rational framework to understand the interactions of engineered nanoscale objects with living systems.

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Credits

Host: Dr Dyani Lewis
Producers: Eric van Bemmel, Kelvin Param
Associate Producer: Dr Dyani Lewis
Audio Engineer: Gavin Nebauer
Voiceover: Nerissa Hannink
Series Creators: Kelvin Param & Eric van Bemmel

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VOICEOVER 
Welcome to Up Close, the research talk show from the University of Melbourne, Australia. 

DYANI LEWIS
I'm Dyani Lewis. Thanks for joining us. Nanotechnology, nanomedicine and nanomaterials have all become familiar terms over recent years, nano referring to the extremely small scale of particles used. As with many new technologies, there has been a mix of both enthusiasm and suspicion that has accompanied nanotechnology's march into the public arena. Nanotechnology has spawned fears of self-replicating nanorobots and asbestos-like fibres that could wreak havoc in our bodies and in the environment. But are these fears justified or are we missing the point of the many benefits that nanotechnology might bring? 
To help us address these questions, we are joined on Up Close today by Professor Kenneth Dawson, a nanotechnology researcher who also has a hand in policy development. Professor Kenneth Dawson is the Director of the Centre for BioNano Interactions and Chair of Physical Chemistry at the School of Chemistry and Chemical Biology at University College Dublin. He also works in an advisory capacity with governments and regulatory bodies looking at nanotechnology standards and regulation. He's a member of several working groups and expert panels across the European Union, the United States and Australia. Welcome to Up Close, Kenneth.

KENNETH DAWSON
Thank you.

DYANI LEWIS
Kenneth, I thought we could start by looking at the development of nanotechnology. How did the field of nanotechnology come about?

KENNETH DAWSON
I think that's a difficult question. I mean it developed bit by bit and in some way, what we now call nanotechnology, or maybe nanoscience, is a realisation of what has happened or what had been happening. Firstly, let me just come back to a point you made that nanotechnology is a science of very small things and just recall that if we all know what a millimetre is, then a nanometre is actually a million times less than a millimetre. So what was really happening through these years, through the 60s, the 70s and 80s is that people were almost unconsciously being able to fabricate smaller and smaller things. Then we began to become aware that there was a set of methods, approaches and ideas that were uniquely associated with that millionth of a millimetre scale.

DYANI LEWIS
So were there particular technological advancements that led to being able to fabricate things at that scale?

KENNETH DAWSON
Yes, I mean again, I think many of them were progressive, though. We simply learned how to make smaller and smaller little reaction vessels and to make nanoparticles, to make smaller and smaller things inside these little capsules. Of course, we shouldn't forget that in parallel the electronics industry was rapidly pushing towards the nanoscale. If you can make pieces of your circuit smaller and smaller, then devices become smaller and smaller and the capacity, let's say to print circuits on the nanometre scale, began to become very important. You know, if you make very small circuits, the electrons have to travel shorter distances before they get to their place, they don't bump into as many things, so that means things work faster and because bumping into things along the way is what causes a lot of heat, you save energy and your computers work faster. So there were these parallel developments all towards the small. 

DYANI LEWIS
You talked about some of the motivations in other areas of nanotechnology, what are some of those?

KENNETH DAWSON
Nowadays I think there is a much clearer vision of what nanotechnology is and I think that's really what has changed. The toolkit began to develop and then we suddenly realised that we could do so many new things. Let me give you an example. Particles, when they become less than about 100 nanometres - that's about 100 of those little millionth of a millimetre things, they begin to engage with our bodies in new ways. We begin to be able to see them and to process them and then we begin to have the possibility, at least, to be able to send those particles to special locations in our bodies, that we'll be able to post medicines, to precise locations rather than what we do at the minute. What we do at the minute is almost an accident of the German dye industry, sort of at the end of the 1800s. 
In those days, chemists were making lots of molecules and it was found that some of those had a therapeutic benefit, but basically when we put a molecule into our bodies, a simple molecule, a drug molecule, it sort of dissolves in different organs. We expend huge effort to try to get that molecule to go to the right place - billions of dollars. Now what we've realised is that if instead of just using our bodies as test tubes, we actually make little particles of the right size, we can actually target them, deliver them to specific locations. So that's one are where we have very specific ideas of what to do with them, but there are so many.

DYANI LEWIS
So what was the public's early reaction to nanotechnology?

KENNETH DAWSON
I think the early public reaction was probably more unsure rather than negative. There were some reports that raised concerns and I think most studies still show that the public is open minded, let's say non-judgemental, but you know, needs to be convinced of everything that we do, which by the way, is quite the right thing to be. I'm also a member of the public. 

DYANI LEWIS
So, Kenneth, could you tell us in what ways we are most likely to come into contact with nanoparticles both in our environment and also in some of the consumer products that we use and consume?

KENNETH DAWSON
Right. So the first thing I think we've really got to understand is that the most usual way to come into contact with them is to come into contact with yourself. You are full of nanoparticles. All of your proteins are nanoparticles. The most common protein in your bloodstream is albumin; it's six nanometres, it's a perfect nanoparticle. That's what I'd alluded to earlier, that getting down to that size is very interesting for new medicines because that's a size where things work in your body. 
So you are composed of nanoparticles but there are all sorts of other areas where you'll come in touch with natural nanoparticles in various dusts, dust from rocks, from volcanoes, at the seaside, aerosols that have dried can produce nanoparticles in the dust in the air. These are natural nanoparticles. In consumer products we are coming in contact now with nanoparticles for example coatings, a lot of coatings for windows, they prevent the sun coming through the window and damaging us or other things. There are all sorts of coatings to protect outside structures now, for example. We also come in contact with nanoparticles in sunscreens and all sorts of other food products and so forth.

DYANI LEWIS
You must have come across some fairly outlandish fears about the synthetic nanoparticles that are becoming more part of modern life.

KENNETH DAWSON
I think one should split the concerns that we come across into two broad classes - outlandish ones and ones that are not outlandish that need to be dealt with. So let's first turn to the question of outlandish. You know, nanobots and robots taking over our minds and so forth, that's just not on the cards right now and it's hard to see how it could be in any foreseeable manifestation of the future. So we tend not to get too worried about those things. Where we focus a lot of our attention is in credible concerns and I think it has to be said that, as with all new technology, the novelty means that there are unanswered questions and those have to be pursued. One thing that has struck me often in this discussion is how we tend to forget comparable concerns about old technologies and we tend not to look back. 
Often these old technologies were introduced at a time when we were less knowledgeable and less careful. There's an important trade-off here that we think about whether these new technologies in some cases, whilst accepting that the risks need to be carefully considered, in many cases could be safer than the ones that we accept without question. Let me give you a few examples. Cars are dangerous and they kill a lot of people on the roads. Now we worked hard over the last decades to improve their safety in all sorts of ways. Everything from the way the front of the car folds up and bags are inflated and so on and so forth. You can see systematic improvements in safety being made but there's no doubt that cars are dangerous. 
Similarly, many chemicals in the environment have been progressively removed from the market over years. Pesticides, chemicals for domestic use, as we've just learned more, these things have been taken away. I think there's a temptation when we are faced with some new technology where we do have to do that work to be sure that it's safe, to forget that all of these things have and have had an associated risks. There's nothing new here. We're just dealing with something that we've always dealt with, is change, novelty, technology - got to be careful, got to look into these questions.

DYANI LEWIS
What about the trade-off between I guess, being cautious of introducing a new technology versus, I guess, maintaining an old and perhaps a dangerous technology?

KENNETH DAWSON
Yes, I think that's a really good question. Here's where I think you begin to see that the nanotechnology discussion is not one discussion, it's many separate discussions. We're pretty convinced that nanotechnology is the route to safety in medicine. Let me tell you why. I alluded to this earlier: the big battle with drug molecules is that they often tend to go to the wrong place. Often they tend to go to the liver. That's why you're told to pop two pills and not five and if you pop five you get sick, if you pop 10 then you end up in hospital. What's happening is that the molecules in that pill are going to the wrong place and they can kill your liver or they can kill something else. That is a consequence of molecules tending to spread throughout our bodies without control. We know for certain, and we have evidence to show that we can target small particles of comparable sizes to proteins to specific locations in your body. This is not a surprise; this is the way your body works. 
So what we're really aware of in being able to work in the nanometre scale in medicine is that, for the first time, mankind is able to work with your body. It's actually able to use what we call endogenous, that is the intrinsic processes. So there's a debate that I think is completely separate from some of the others. No doubt, when we get it right, nanotechnology is the route to safety. You take another example, which I think is much less clear: silver nanoparticles in socks. Is that prudent? Is it necessary? What real benefits are coming from that? If we convince ourselves that silver nanoparticles do suppress undesirable bacteria or say, resistant bacteria, many of us believe that that is the case - then there's a credible application of silver nanoparticles in hospitals for patients with low immune responses facing difficulties. That's a very credible use. But I think many have questioned the use, the careless or - I've heard the word just in the last few days from a colleague - frivolous use - of nanoparticles. These are two completely different debates.

DYANI LEWIS
I'm Dyani Lewis. My guest today is chemist and nanotechnology researcher Professor Kenneth Dawson and we're talking about nanotechnology here on Up Close. Kenneth, nanomaterials are the product of the physical sciences, in many ways. Why is it important to approach nanotechnology from a biological perspective?

KENNETH DAWSON
That's a really good question, too. Nanotechnology was driven, conceived, the energy for the drive from it came from the physical and material sciences. In those early days, material scientists or physicists or chemists would know enough biology to really be able to work at the interface. That's changing. These generations of students coming through now, they begin to really see knowledge as a continuum and we've been able to break down some of these barriers. The real reason that it's important in our field is that we have no particular desire to make any old nanoparticle. We're trying to solve problems. 
Our long-term aim is to cure very, very difficult diseases. Our middle-term aim is to reduce the amounts of drugs that we have to give to people for existing diseases. So we need to know how those particles that we're designing interact in biological systems. We need to take a step back, forget the physics, forget the chemistry, forget the biology, forget the medicine. It's all about what challenges do we face, what big, big challenges do we face in our society? How can we confront them?

DYANI LEWIS
So, starting with the biological problem rather than starting with hey, here's a new material, what can we use it for?

KENNETH DAWSON
Yeah, I think that's the way forward. Now, that's not to say that these initial years - I mean they were beneficial and you have to understand that science is not a linear process. So of course there was a sort of an effusion of knowledge and results of people saying oh, I can make this, so I just make it, and that's good, there's no harm in that. But I think we come now to a phase where we recognise, you know, we can do anything, what should we do? I think you can now see that convergence of awareness in our scientific society. 
What are the big problems we face in our society? Health, environment - is it possible, for example, to significantly reduce the amount of pesticides in our environment, the amount of fertilisers in our environment? Can we, for example, package up pesticides into smaller packages, release them more slowly, so that we can reduce the amount we release into the environment by a hundred? Can we reduce by a thousand? 
That's the question of today. The question of tomorrow will be can we get rid of those kinds of pesticides altogether? Can we begin to work better with nature? After all, nature is, as I said, a big nanoparticle-processing device. So maybe we don't really need chemicals, but that's a dream.

DYANI LEWIS
How easy is it to predict how a material will behave, given what we know about a material at a non-nano scale? For example, gold being a fairly inert substance, does that tell us much about how that material will behave at the nano level?

KENNETH DAWSON
It tells us a lot, but we shouldn't think it tells all. Here, I come back to the measured, cautious side of this discussion. Whilst it's certainly true that there have been a lot of wild claims and fears, nevertheless it is true that when things become this small, some of their properties change. It is necessary for us to study those questions. It is not always possible to predict the properties of those materials simply on their bulk properties. It may surprise you to know - if you take the case of silver - a very simple example - that silver always dissolves very, very slowly. Now, you don't notice that much over a generation of silverware. Well, if you happen to be lucky enough to own silverware these days, with real silver. But anyway, you wouldn't notice that, you'd notice over several generations, actually, by the way. I have some of my grandmother's silver so I can sort of see it's thinned a bit. 
But anyway, if you look at silver nanoparticles, they actually dissolve relatively quickly. That's simply because there's so much surface compared to the amount of substance so they can dissolve much more quickly. Lots of new properties when things get really small, need to think about it, need to study it. 

DYANI LEWIS
Now, your research looks at the toxicological effects of nanoparticles. Could you describe the kinds of experiments that you conduct to look at nanomaterial toxicity?

KENNETH DAWSON
We do look somewhat at toxicological issues. I'm the Director of the European Centre for what's called NanoSafety and there are many corresponding laboratories throughout Europe and the world that check toxicological features, but actually a lot of what we do is try to understand how nanoparticles work in living organisms. I think that's an important distinction because toxicology as such, was built around known hazards, the hazards of the past, was built around the hazards of drugs, the hazards of chemicals. I think we've always been aware since we entered this field, that whilst that has to be done, and it has to be done carefully, it can be done well and by many people. 
The hard questions would be ones like are there radically new things that happen with nanoparticles that don't happen with bulk materials or with chemicals and could they introduce new kinds of hazards? So we tend to look at really, details, we look at what the surface of the nanoparticle looks like when it's inside a cell. We ask where it's going inside the cell, why it's going there. We ask will it cross a barrier, say a barrier of the lungs, a barrier of the brain, and what would that imply if it did. So it's more those kind of questions that, in my own research group that we focus on. But we do have this broader role about toxicity across Europe.

DYANI LEWIS
I'm Dyani Lewis. My guest today is Professor Kenneth Dawson, a nanotechnology researcher policy advisor. We're talking about nanotechnology and society's response to it, here on Up Close. Kenneth, what sorts of things have you found, I guess, about even differences in different nanoparticles, whether they are natural nanoparticles or synthetic nanoparticles and how the cells respond to those?

KENNETH DAWSON
Well, one thing I should say is that there are of course, toxic nanoparticles and that's not surprising: there are toxic chemicals too. I wouldn't consider those as findings, and they are discussed in the literature and it's an important issue, that there are things that are poisonous. The deeper question is whether materials that have not previously been recognised as toxic could become so, at smaller scales. Typically the answer is we've not found such a thing. We have been discovering that they can traverse - go new places. We've been discovering that they can be managed differently by cells and by biology. But equally, we've been discovering that there are intrinsic biological processes to handle them, including to handle them when they're undesirable or when they're waste. 
That's a very interesting twist of the story that I think is probably too early to go into in too much detail. You see, it comes back to this point that biology is meant to work on the scale of nanometres and therefore it's accustomed to dealing with things like that; it knows what to do. Now, I don't want to be too optimistic and I don't want to say that everything's fine. It's too early to say that, but we can certainly see evidence that organisms have a whole repertoire of dealing with nanoparticles. They've known them forever; they can put them in places and degrade them. They can degrade them effectively, they can clear them, so it'll be interesting perhaps, to look back even on this recording in 10, 20 years' time. There may be a very different view at that point. Nanotechnology may be seen by those that follow us as the route to safety.

DYANI LEWIS
Kenneth, you've also studies something called biomolecular coronas. Could you describe for us what these biomolecular coronas are and what their implications are for nanotechnology?

KENNETH DAWSON
This was really the beginning of us understanding how different a nanoparticle could be in a biological context - or in an organism or in you - than in a laboratory. Succinctly put, when a typical nanoparticle enters a real environment - let me take a very simple example: your blood. It coats itself, it adsorbs to itself a group of molecules - proteins - and that, we believe nowadays, to a large extent, confers it's identity and so we begin to believe, in this field, that we need to think about the identity in situ rather than the identity as made. That's sort of a rapidly evolving are of science and we're making a fair amount of rapid progress. We think we're almost able, in many cases, to read the identity of the particle in these realistic situations.

DYANI LEWIS
So what sort of molecules are adsorbing?

KENNETH DAWSON
Well, it depends on the environment. I mean it would depend, for example, if the particle makes first contact with lung lining fluids, makes contact first with saliva, makes contact first with blood [unclear] bloods and it's proteins, it's lipids, lipoproteins, these sorts of things. There are other small molecules there. These are the things that are really conferring its identity. 

DYANI LEWIS
Kenneth, is nanotechnology currently regulated?

KENNETH DAWSON
Yes and no. It is considered within existing regulations in most jurisdictions. That is, there are very strong regulatory processes in all developed countries that address things like chemicals and within those frameworks, nanoparticles are considered and they're often considered by the explicit actors that are meant to operate those more carefully. Let me explain for a moment what I mean by that. You can have a general regulatory framework, but actually I think what is often missed is that all these frameworks are supported by people, they're supported by agencies that operate the rules and in many ways the outcome depends on who those people are and how well skilled they are and how knowledgeable they are. 
So we find nowadays that the regulatory agencies, even though the rules haven't changed, they take a very close look at what they're being offered within the existing rules. They take a very close look at emerging products and in many cases they do have the tools they need to exercise caution. Now, in certain areas of the world - in Europe, for example - there has been a little bit stronger reaction. The European Commission has proposed a definition of what nano is for regulatory purposes, for example. They've considered that it is less than 100 nanometres. 
That general concept is now cascading down into the agencies and into the regulations and we may expect, I think, some explicit steps to be taken to look more carefully at regulations explicitly for nano. Australia, by the way, is amongst the most advanced countries in the world in regulations. Not only is it very strongly coupled to Europe's considerations and the United States' considerations, but it has itself, within it's agencies, for example the APVMA, the TGA and other agencies here…

DYANI LEWIS
…and APVMA, hat's the Australian Pesticides and Veterinary Medicines Authority, is it? And the TGA the Therapeutic Goods Administrations?

KENNETH DAWSON
They are amongst, I would say, the most advanced agencies in the world in thinking about these issues. 

DYANI LEWIS
Kenneth, thank you for being our guest today on Up Close and discussing your work in the burgeoning field of nanotechnology.

KENNETH DAWSON
Great pleasure.

DYANI LEWIS
Professor Kenneth Dawson is the Director of the Centre for BioNano Interactions and Chair of Physical Chemistry at The School of Chemistry and Chemical Biology at University College, Dublin. Relevant links, a full transcript and more information on this episode can be found on our website at upclose.unimelb.edu.au. Up Close is a production of the University of Melbourne, Australia. This episode was recorded on 29 August 2012. Our producers for this episode were Kelvin Param and Eric Van Bemmel. The associate producer was myself, Dyani Lewis, with audio engineering by Gavin Nebauer. Up Close is created by Eric Van Bemmel and Kelvin Param. Until next time, goodbye.

VOICEOVER 
You've been listening to Up Close. We're also on Twitter and Facebook. For more information visit upclose.unimelb.edu.au copyright 2012, the University of Melbourne.


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